Trial Outcomes & Findings for Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma (NCT NCT01064648)

Last Updated: 2026-04-29

Results Overview

MTD was determined by testing dose-de-escalation to 20mg PO daily on dose de-escalation cohort 1 to 2 with 3 to 6 patients each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. Toxicities will be graded according to the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events. Dose-limiting toxicities (DLT) apply only during Cycle 1 and must be drug-related (i.e. possibly, probably or definitely related to one of the 3 study drugs). The following events occurring in the first cycle of treatment are considered dose limiting. 1. Febrile neutropenia 2. Grade 4 neutrophil count decrease for more than 7 days' duration 3. Grade 4 platelet count decrease 4. Grade 3 or 4 non-hematologic toxicity (excluding alopecia)

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

117 participants

Primary outcome timeframe

Weekly during first cycle (1cycle = 21 days). Then will be reported every cycle while patient is on treatment.

Results posted on

2026-04-29

Participant Flow

117 participants were enrolled, only 112 participants were included in the analysis: 5 patients were either not eligible or not analyzable. Thus these 5 patients were excluded from any analysis.

Participant milestones

Participant milestones
Measure	Phase I Cisplatin-pemetrexed Cediranib 30mg Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase I Cisplatin-pemetrexed Cediranib 20mg Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV Placebo: Given orally	Phase II Cisplatin-pemetrexed Cediranib 20mg Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Phase I Cohort1: Dose Level 1 STARTED	7	0	0	0
Phase I Cohort1: Dose Level 1 COMPLETED	0	0	0	0
Phase I Cohort1: Dose Level 1 NOT COMPLETED	7	0	0	0
Phase I Cohort 2: Dose Level 2 STARTED	0	13	0	0
Phase I Cohort 2: Dose Level 2 COMPLETED	0	0	0	0
Phase I Cohort 2: Dose Level 2 NOT COMPLETED	0	13	0	0
Phase II STARTED	0	0	49	48
Phase II COMPLETED	0	0	0	0
Phase II NOT COMPLETED	0	0	49	48

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Cisplatin-pemetrexed Cediranib 30mg Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase I Cisplatin-pemetrexed Cediranib 20mg Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV Placebo: Given orally	Phase II Cisplatin-pemetrexed Cediranib 20mg Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Phase II Death	0	0	4	5
Phase II Withdrawal by Subject	0	0	2	5
Phase II Progression	0	0	21	27
Phase II Non-protocol specified	0	0	5	3
Phase II Under Review	0	0	2	0
Phase I Cohort1: Dose Level 1 Progression	5	0	0	0
Phase I Cohort1: Dose Level 1 Non-protocol specified	2	0	0	0
Phase I Cohort 2: Dose Level 2 Adverse Event	0	3	0	0
Phase I Cohort 2: Dose Level 2 Withdrawal by Subject	0	1	0	0
Phase I Cohort 2: Dose Level 2 Progression	0	5	0	0
Phase I Cohort 2: Dose Level 2 Non-protocol specified	0	4	0	0
Phase II Adverse Event	0	0	15	8

Baseline Characteristics

Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I All Participants n=20 Participants All participants from Phase I	Phase II Cisplatin-pemetrexed Cediranib 20mg n=45 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=47 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Total n=112 Participants Total of all reporting groups
Age, Continuous	64.4 years n=9 Participants	71.3 years n=24 Participants	71.8 years n=23 Participants	69.8 years n=73 Participants
Sex: Female, Male Female	5 Participants n=9 Participants	7 Participants n=24 Participants	7 Participants n=23 Participants	19 Participants n=73 Participants
Sex: Female, Male Male	15 Participants n=9 Participants	38 Participants n=24 Participants	40 Participants n=23 Participants	93 Participants n=73 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=9 Participants	3 Participants n=24 Participants	2 Participants n=23 Participants	6 Participants n=73 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=9 Participants	41 Participants n=24 Participants	44 Participants n=23 Participants	104 Participants n=73 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	1 Participants n=24 Participants	1 Participants n=23 Participants	2 Participants n=73 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants
Race (NIH/OMB) Asian	2 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	2 Participants n=73 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants
Race (NIH/OMB) Black or African American	2 Participants n=9 Participants	1 Participants n=24 Participants	3 Participants n=23 Participants	6 Participants n=73 Participants
Race (NIH/OMB) White	15 Participants n=9 Participants	43 Participants n=24 Participants	42 Participants n=23 Participants	100 Participants n=73 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=9 Participants	1 Participants n=24 Participants	2 Participants n=23 Participants	4 Participants n=73 Participants
Zubrod Performance Status 0-1	19 Participants n=9 Participants	42 Participants n=24 Participants	44 Participants n=23 Participants	105 Participants n=73 Participants
Prior history of definitive surgery No	17 Participants n=9 Participants	33 Participants n=24 Participants	41 Participants n=23 Participants	91 Participants n=73 Participants
Zubrod Performance Status 2	1 Participants n=9 Participants	3 Participants n=24 Participants	3 Participants n=23 Participants	7 Participants n=73 Participants
Histology Epitheliod or mesothelioma, NOS	18 Participants n=9 Participants	34 Participants n=24 Participants	35 Participants n=23 Participants	87 Participants n=73 Participants
Histology Biphasic or sarcomatoid	2 Participants n=9 Participants	11 Participants n=24 Participants	12 Participants n=23 Participants	25 Participants n=73 Participants
Prior history of radiation Yes	5 Participants n=9 Participants	8 Participants n=24 Participants	9 Participants n=23 Participants	22 Participants n=73 Participants
Prior history of radiation No	15 Participants n=9 Participants	37 Participants n=24 Participants	38 Participants n=23 Participants	90 Participants n=73 Participants
Prior history of definitive surgery Yes	3 Participants n=9 Participants	12 Participants n=24 Participants	6 Participants n=23 Participants	21 Participants n=73 Participants
Measurable Disease per RECIST 1.1 Measurable	17 Participants n=9 Participants	35 Participants n=24 Participants	40 Participants n=23 Participants	92 Participants n=73 Participants
Measurable Disease per RECIST 1.1 Non-measurable	3 Participants n=9 Participants	10 Participants n=24 Participants	7 Participants n=23 Participants	20 Participants n=73 Participants
Measurable Disease per Modified RECIST for Pleural Tumors Measurable	19 Participants n=9 Participants	36 Participants n=24 Participants	30 Participants n=23 Participants	85 Participants n=73 Participants
Measurable Disease per Modified RECIST for Pleural Tumors Non-measurable	1 Participants n=9 Participants	9 Participants n=24 Participants	17 Participants n=23 Participants	27 Participants n=73 Participants

PRIMARY outcome

Timeframe: Weekly during first cycle (1cycle = 21 days). Then will be reported every cycle while patient is on treatment.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=20 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Maximum Tolerated Dose of Cediranib in Combination With Cisplatin and Pemetrexed (Phase I)	20 mg	—

PRIMARY outcome

Timeframe: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever came first, assessed up to 5 years.Disease assessment will be repeated every 6 weeks until disease progression.

Population: Only eligible and analyzable patients were included.

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesions, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=45 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=47 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Progression-free Survival (Phase II)	7.2 month Interval 5.5 to 8.5	5.6 month Interval 4.6 to 6.2

SECONDARY outcome

Timeframe: From date of registration to death.Disease assessment will be repeated every 6 weeks until disease progression. After progression, follow up will occur every 6 months for the first two years and then at the end of the third year after registration.

Population: Only eligible and analyzable patients are included in the analysis.

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=45 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=47 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Overall Survival (Phase II)	10 month Interval 7.7 to 13.5	8.5 month Interval 6.6 to 13.8

SECONDARY outcome

Timeframe: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years. Best response is documented for as long as the patient remains on protocol treatment.

Population: Only eligible patients with baseline measurable disease per RECIST 1.1 were included in the analysis.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=35 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=40 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Response Rate by RECIST1.1 (Phase II)	26 percentage of analyzed participants Interval 12.0 to 43.0	15 percentage of analyzed participants Interval 6.0 to 30.0

SECONDARY outcome

Timeframe: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control rate is documented for as long as the patient remains on protocol treatment.

Population: Eligible patients with baseline eligible disease per RECIST 1.1 were included in the analysis.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA): Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA All target measurable lesions must be assessed using the same techniques as baseline.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=35 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=40 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Disease Control Rate by RECIST 1.1 (Phase II)	74 percentage of analyzed participants Interval 57.0 to 88.0	80 percentage of analyzed participants Interval 64.0 to 91.0

SECONDARY outcome

Timeframe: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Best response is documented for as long as the patient remains on protocol treatment.

Population: Eligible patients with baseline measurable disease per modified RECIST were included in the analysis.

Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=36 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=30 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Response Rate by Modified RECIST (Phase II)	50 percentage of analyzed participants Interval 33.0 to 67.0	20 percentage of analyzed participants Interval 8.0 to 39.0

SECONDARY outcome

Timeframe: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control is documented for as long as the patient remains on protocol treatment.

Population: Eligible patients with baseline measurable disease per modified RECIST were included in the analysis.

Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA), does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA. All target measurable lesions must be assessed using the same techniques as baseline.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=36 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=30 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Disease Control Rate by Modified RECIST (Phase II)	75 percentage of analyzed participants Interval 58.0 to 88.0	83 percentage of analyzed participants Interval 65.0 to 94.0

SECONDARY outcome

Timeframe: Toxicity assessment is repeated weekly during first cycle (1cycle = 21 days), then every cycle while patient is on treatment.

Population: Patients who received at least one dose of protocol treatment.

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=7 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=13 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Palmar-plantar erythrodysesthesia syndrome	1 Participants	0 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Peripheral sensory neuropathy	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	0 Participants	3 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pulmonary hypertension	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	0 Participants	2 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Weight loss	1 Participants	0 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Gastrointestinal disorders - Other, specify	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Heart failure	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypertension	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypokalemia	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypomagnesemia	1 Participants	0 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyponatremia	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Irregular menstruation	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	2 Participants	0 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Mucositis oral	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nervous system disorders - Other, specify	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	1 Participants	2 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	2 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Abdominal pain	0 Participants	2 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anemia	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Constipation	0 Participants	1 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dehydration	0 Participants	3 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	2 Participants	2 Participants
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Toxicity assessment is repeated every 3 weeks while patient is on treatment.

Population: Patients who received at least one dose of protocol treatment.

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Phase II Cisplatin-pemetrexed Cediranib 20mg n=44 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. Cediranib Maleate: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Phase II Cisplatin-pemetrexed Placebo n=44 Participants Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. Placebo: Given orally Cisplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Acute coronary syndrome	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anemia	1 Participants	7 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anorexia	7 Participants	4 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Atrial fibrillation	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Atrial flutter	1 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Chest wall pain	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Creatinine increased	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Death NOS	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dehydration	4 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Delirium	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Duodenal hemorrhage	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	2 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Epistaxis	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fall	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	6 Participants	5 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs General disorders and admin site conditions-Other	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Generalized muscle weakness	1 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Glucose intolerance	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Headache	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hearing impaired	0 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Heart failure	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyperglycemia	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypertension	9 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypocalcemia	1 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypokalemia	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypomagnesemia	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyponatremia	5 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypotension	3 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Intracranial hemorrhage	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	1 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	2 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Mucositis oral	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	4 Participants	5 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	6 Participants	8 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Non-cardiac chest pain	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Peripheral sensory neuropathy	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	4 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash maculo-papular	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Renal and urinary disorders - Other, specify	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Respiratory failure	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Seizure	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Sinus bradycardia	2 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Supraventricular tachycardia	1 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Syncope	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Thromboembolic event	3 Participants	3 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Urinary tract infection	0 Participants	1 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	0 Participants	2 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Weight loss	4 Participants	0 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	3 Participants	4 Participants
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Wound dehiscence	1 Participants	0 Participants

Adverse Events

Phase I Cisplatin-pemetrexed Cediranib 30mg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 7 deaths

Phase I Cisplatin-pemetrexed Cediranib 20mg

Serious events: 6 serious events

Other events: 13 other events

Deaths: 9 deaths

Phase II Cisplatin-pemetrexed Cediranib 20mg

Serious events: 32 serious events

Other events: 42 other events

Deaths: 39 deaths

Phase II Cisplatin-pemetrexed Placebo

Serious events: 25 serious events

Other events: 43 other events

Deaths: 41 deaths

Serious adverse events

Other adverse events

Additional Information

SWOG statistician

SWOG Statistics & Data Management Center

Phone: 2066674263

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60