Trial Outcomes & Findings for Gemcitabine With or Without Pazopanib in Treating Patients With Refractory Soft Tissue Sarcoma (NCT NCT01532687)

Last Updated: 2021-09-27

Results Overview

Compared using a one-sided Gehan-Wilcoxon test stratified by sarcoma subtype. Kaplan-Meier estimates for each treatment arm will be presented with the estimated hazard ratios and their associated confidence intervals. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 as at least a 20% increase in the sum of the longest diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5 mm (target lesions), or measurable increase in non-target lesions (unequivocal progression), or appearance of one or more new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Calculated as the time from randomization to the first documented progression or death, whichever occurs first, or until time of last contact if no progression or death occurred, assessed up to 3 years

Results posted on

2021-09-27

Participant Flow

Double-blinded randomization (1:1) was stratified by subtypes of sarcoma (liposarcoma vs. all other eligible soft tissue sarcoma subtypes). Patients were randomized to either experimental arm or placebo arm prior to starting treatment. Those who discontinued treatment on the placebo arm due to disease progression were eligible for treatment with open-label pazopanib (unblinded, cross-over treatment); those who developed disease progression on the Experimental arm (pazopanib arm) were not.

Participant milestones

Participant milestones
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Overall Study STARTED	29	25
Overall Study Crossover to Open-label Pazopanib	0	14
Overall Study COMPLETED	15	23
Overall Study NOT COMPLETED	14	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Overall Study Death	2	0
Overall Study Adverse Event	6	1
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	2	1
Overall Study Protocol-defined delay > 3 weeks	3	0

Baseline Characteristics

Gemcitabine With or Without Pazopanib in Treating Patients With Refractory Soft Tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO	Total n=54 Participants Total of all reporting groups
Age, Continuous	63 years n=99 Participants	56 years n=107 Participants	60 years n=206 Participants
Sex: Female, Male Female	14 Participants n=99 Participants	16 Participants n=107 Participants	30 Participants n=206 Participants
Sex: Female, Male Male	15 Participants n=99 Participants	9 Participants n=107 Participants	24 Participants n=206 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized White	25 Participants n=99 Participants	24 Participants n=107 Participants	49 Participants n=206 Participants
Race/Ethnicity, Customized Unknown/Not Reported	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Histology Liposarcoma	9 Participants n=99 Participants	7 Participants n=107 Participants	16 Participants n=206 Participants
Histology Leiomyosarcoma (LMS)	9 Participants n=99 Participants	5 Participants n=107 Participants	14 Participants n=206 Participants
Histology Undifferentiated Pleomorphic Sarcoma (UPS)	3 Participants n=99 Participants	5 Participants n=107 Participants	8 Participants n=206 Participants
Histology Synovial Sarcoma	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Histology Other Sarcoma(s)	5 Participants n=99 Participants	5 Participants n=107 Participants	10 Participants n=206 Participants
Number Prior Treatments	1 Treatments n=99 Participants	1 Treatments n=107 Participants	1 Treatments n=206 Participants

PRIMARY outcome

Timeframe: Calculated as the time from randomization to the first documented progression or death, whichever occurs first, or until time of last contact if no progression or death occurred, assessed up to 3 years

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Progression-free Survival (PFS) All randomized	4.5 months Interval 3.0 to 8.5	1.6 months Interval 1.4 to 4.3
Progression-free Survival (PFS) Liposarcoma	8.9 months Interval 4.3 to There were not sufficient events to define the upper limit of the confidence interval (two out of nine participants progressed)	1.5 months Interval 1.0 to Due to the small sample size (n = 7) the upper confidence limit was not estimable (did not cross the 50% line)
Progression-free Survival (PFS) Other Sarcoma	4.4 months Interval 3.0 to 8.8	2.2 months Interval 1.4 to 4.6

SECONDARY outcome

Timeframe: Calculated as the time from receiving open-labeled pazopanib hydrochloride to the next documented progression or death whichever occurs first, assessed up to 3 years

Population: Participants randomized to the gemcitabine + placebo arm who progressed and elected to receive gemcitibine + open-label pazopanib

Participants who progress during treatment and are found to be part of the gemcitabine+placebo arm after unblinding are eligible to receive open-label pazopanib with gemcitabine. This is the crossover population. Statistical analysis is exploratory and requires sufficient crossover participants to assess Kaplan-Meier estimated hazard ratio and associated 95% confidence interval. This represents the participants second progression. In both cases progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 as at least a 20% increase in the sum of the longest diameters of target lesions with an absolute increase of at least 5 mm (target lesions), or measurable increase in non-target lesions (unequivocal progression), or appearance of one or more new lesions. First progression uses the smallest sum on study as a reference; progression for the crossover population uses first progression measurements as the reference.

Outcome measures

Outcome measures
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=14 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Progression-free Survival (PFS) for a Sub-group of Patients Treated With Open-label Pazopanib Hydrochloride Following Administration of Gemcitabine Hydrochloride in the Cross-over Portion of This Study	3.0 months Interval 1.3 to Due to the small sample size (n = 14) the upper confidence limit was not estimable (did not cross the 50% line)	—

SECONDARY outcome

Timeframe: Best overall objective response recorded from the start of treatment until disease progression/recurrence assessed up to 3 years

Population: All randomized participants.

Response is evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where RECIST combines assessments for target, non-target and presence of new lesions. Best Overall Objective Response is the sum of all CR+PR divided by all randomized participants, where the strongest recorded response is used for the evaluation (CR\>PR\>SD\>PD). Objective response (CR+PR) requires at least a 30% decrease in the sum of the largest diameter target lesions (with respective to the baseline sum); disappearance of all or persistence of one or more non-target lesions, maintenance of tumor marker levels above normal limits, and no new lesions. Estimated odds ratio of best overall objective response are reported with 95% confidence interval for the two histologic sarcoma subgroups (liposarcoma vs all other eligible soft tissue sarcoma subtypes). One-sided proportions test is used to determine whether best overall objective response is greater for the gemcitabine plus pazopanib group.

Outcome measures

Outcome measures
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Percentage of Participants Achieving Best Overall Objective Response (CR+PR) All randomized participants	6.9 percentage of participants Interval 0.9 to 22.8	8.0 percentage of participants Interval 1.0 to 26.0
Percentage of Participants Achieving Best Overall Objective Response (CR+PR) Liposarcoma participants	22.2 percentage of participants Interval 2.8 to 60.0	0 percentage of participants No participants achieved overall objective response, making the confidence interval not estimable
Percentage of Participants Achieving Best Overall Objective Response (CR+PR) Other sarcoma participants	0 percentage of participants No participants achieved overall objective response, making the confidence interval not estimable	11.1 percentage of participants Interval 1.4 to 34.7

SECONDARY outcome

Timeframe: From randomization to death due to any cause, or until last patient contact if the patient did not die, assessed up to 3 years

Population: All randomized participants

Two treatment arms will be compared using a one-sided log-rank test stratified by sarcoma subtype and study site. Kaplan-Meier estimates and the survival curves for each treatment arm will be presented with the estimated hazard ratios and their associated confidence interval.

Outcome measures

Outcome measures
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 Participants Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may receive single-agent pazopanib hydrochloride PO daily. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO
Overall Survival All Randomized	11.0 months Interval 9.6 to 20.7	15.6 months Interval 6.1 to 27.0
Overall Survival Liposarcoma participants	20.5 months Interval 11.0 to Upper limit was not estimable because there was no observed death time greater than the median survival that touched or crossed -1,96 using the log-transformation of the survival function (ref: Formula 4.5.5, Klein JP and Moeschberger ML, Survival Analysis: Techniques for censored and truncated data). This is likely due to small sample size (n = 9).	5.7 months Interval 3.5 to Upper limit was not estimable due to small sample size (n = 7) and failure to cross the 25% line.
Overall Survival Other Sarcoma participants	10.2 months Interval 7.6 to 20.7	17.7 months Interval 7.6 to 30.7

Adverse Events

Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride

Serious events: 8 serious events

Other events: 25 other events

Deaths: 23 deaths

Gemcitabine Hydrochloride Plus Placebo

Serious events: 6 serious events

Other events: 14 other events

Deaths: 10 deaths

Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib

Serious events: 5 serious events

Other events: 9 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Christopher Ryan

OHSU Knight Cancer Institute

Phone: 503-494-9000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 participants at risk Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 participants at risk Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression, are unblinded and found randomized to placebo arm may crossover to receive open-label pazopanib hydrochloride PO daily. AEs and deaths reported only while participant is in placebo arm/group. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO	Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib n=14 participants at risk Patients who progress and found randomized to the placebo arm after unblinding are eligible for receipt of open-label gemcitabine plus pazopanib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. AEs and deaths collected during this treatment period
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Alanine aminotransferase increased	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Aspartate aminotransferase increased	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Hepatobiliary disorders Cholecystitis	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Dyspnea	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Blood and lymphatic system disorders Febrile neutropenia	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Gastrointestinal disorders Gastric perforation	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Cardiac disorders Heart failure	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Hepatobiliary disorders Hepatic failure	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Vascular disorders Hypertension	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
General disorders Pain	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Renal and urinary disorders Proteinuria	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Infections and infestations Skin infection	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Cardiac disorders Supraventricular tachycardia	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Vascular disorders Thromboembolic event	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Ejection fraction decreased	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Cardiac disorders Acute coronary syndrome	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Infections and infestations Lung infection	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Cardiac troponin I increase	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Gastrointestinal disorders Colitis	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
General disorders Fever	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Neutrophil count decreased	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Platelet count decreased	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
General disorders Edema limbs	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
General disorders Edema trunk	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Cardiac disorders Atrial fibrillation	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)

Other adverse events
Measure	Gemcitabine Hydrochloride Plus Pazopanib Hydrochloride n=29 participants at risk Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO	Gemcitabine Hydrochloride Plus Placebo n=25 participants at risk Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and placebo PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression, are unblinded and found randomized to placebo arm may crossover to receive open-label pazopanib hydrochloride PO daily. AEs and deaths reported only while participant is in placebo arm/group. Gemcitabine: Given IV Gemcitabine Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib: Given PO Pazopanib Hydrochloride: Given PO Placebo Administration: Given PO	Crossover From Gemcitabine Plus Placebo to Gemcitabine Plus Open-label Pazopanib n=14 participants at risk Patients who progress and found randomized to the placebo arm after unblinding are eligible for receipt of open-label gemcitabine plus pazopanib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and pazopanib hydrochloride PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. AEs and deaths collected during this treatment period
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	14.3% 2/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Alanine aminotransferase increased	10.3% 3/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Blood and lymphatic system disorders Anemia	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	12.0% 3/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Aspartate aminotransferase increased	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Gastrointestinal disorders Diarrhea	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
General disorders Fatigue	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	14.3% 2/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Blood and lymphatic system disorders Febrile neutropenia	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	8.0% 2/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Cardiac disorders Heart failure	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Metabolism and nutrition disorders Hyperglycemia	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Vascular disorders Hypertension	17.2% 5/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Metabolism and nutrition disorders Hypoalbuminemia	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	14.3% 2/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Metabolism and nutrition disorders Hypophosphatemia	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Lymphocyte count decreased	13.8% 4/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Neutrophil count decreased	41.4% 12/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	36.0% 9/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Platelet count decreased	13.8% 4/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Vascular disorders Thromboembolic event	10.3% 3/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations White blood cell decreased	13.8% 4/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	4.0% 1/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Investigations Ejection fraction decreased	6.9% 2/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Hepatobiliary disorders Cholecystitis	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Dyspnea	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Gastrointestinal disorders Gastric perforation	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Metabolism and nutrition disorders Hyponatremia	3.4% 1/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/29 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	0.00% 0/25 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)	7.1% 1/14 • Adverse events were collected up 30 days after the last dose of study drugs while participant was in that Arm/Group. All-Cause Mortality was assessed up to 3 years. For SAEs and OAEs, the Gem+Pazo group was assessed up to 32.1 months; Gem+Placebo participants were assessed up to 36.0 months (30 days after progression). If Gem+Placebo participants crossed over to open-label Pazo after progression, any additional AEs were collected under the crossover arm (up to 16.6 months). All Serious Adverse Events (SAEs) are reported, irrespective of grade or attribution. For other Adverse Events (AEs), only those grade 3 or higher are collected with a threshold set at 3.5% within any arm. AEs and SAEs are assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Assessments are made by laboratory tests, physical exam, and other clinical measurements (e.g. ECGs, radiological scans, vital signs, etc.)