Trial Outcomes & Findings for Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma: (NCT NCT02348008)
NCT ID: NCT02348008
Last Updated: 2022-09-14
Results Overview
To establish the maximum tested safe dose of bevacizumab in combination with 200mg of MK-3475(pembrolizumab) for subjects with metastatic clear cell renal carcinoma after failure of at least one systemic therapy for metastatic disease.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
61 participants
Primary outcome timeframe
Every 21 days while on treatment (estimated 4 months)
Results posted on
2022-09-14
Participant Flow
Participant milestones
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV;
|
Arm A - Phase Ib Dose Ecalation Cohort 2
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
10
|
48
|
|
Overall Study
COMPLETED
|
0
|
0
|
29
|
|
Overall Study
NOT COMPLETED
|
3
|
10
|
19
|
Reasons for withdrawal
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV;
|
Arm A - Phase Ib Dose Ecalation Cohort 2
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
3
|
|
Overall Study
Disease Progression
|
1
|
5
|
16
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
|
Overall Study
Symptomatic Deterioration
|
0
|
1
|
0
|
Baseline Characteristics
Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma:
Baseline characteristics by cohort
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
n=48 Participants
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
n=99 Participants
|
61 years
n=107 Participants
|
60 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
45 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=99 Participants
|
48 participants
n=107 Participants
|
61 participants
n=206 Participants
|
|
Karnofsky Performance Status (KPS)
KPS 70
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Karnofsky Performance Status (KPS)
KPS 80
|
3 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Karnofsky Performance Status (KPS)
KPS 90
|
1 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Karnofsky Performance Status (KPS)
KPS 100
|
7 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Prior Nephrectomy
Yes
|
11 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
54 Participants
n=206 Participants
|
|
Prior Nephrectomy
No
|
2 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Bone Metastases
Yes
|
6 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Bone Metastases
No
|
7 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Metastatic RCC Prognosis (by IMDC/Heng Score)
Favorable
|
5 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Metastatic RCC Prognosis (by IMDC/Heng Score)
Intermediate
|
3 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Metastatic RCC Prognosis (by IMDC/Heng Score)
Poor
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Every 21 days while on treatment (estimated 4 months)To establish the maximum tested safe dose of bevacizumab in combination with 200mg of MK-3475(pembrolizumab) for subjects with metastatic clear cell renal carcinoma after failure of at least one systemic therapy for metastatic disease.
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Phase 1b: Maximum Safe Dose of Treatment Regimen
|
15 mg/kg
|
—
|
PRIMARY outcome
Timeframe: Every 6 weeks while on treatment (estimated 10 months)Population: Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
To determine the activity of combination of MK-3475 and bevacizumab in first line therapy for subjects with treatment naïve metastatic clear cell RCC as assessed by response rates (complete or partial response) By calculating the proportion of subjects with a response (CR, PR) based on RECIST 1.1 where: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
n=48 Participants
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Overall Response Rate
|
41.7 percentage of participants
Interval 15.2 to 72.3
|
60.9 percentage of participants
Interval 45.4 to 74.9
|
SECONDARY outcome
Timeframe: Up to two years from enrollmentPopulation: Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
To determine median progression-free survival (PFS) for this patient population, per RECIST 1.1 where: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
n=47 Participants
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Progression-Free Survival
|
9.9 months
Interval 4.9 to 16.7
|
20.7 months
Interval 11.3 to 27.4
|
SECONDARY outcome
Timeframe: Up to 2 years from registrationPopulation: Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
To determine if treatment regimen improves overall survival for this patient population. Median overall survival will be calculated up to 2 years from registration.
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
n=47 Participants
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Overall Survival
|
17.9 Months
Interval 6.3 to
95% confidence interval upper limit not estimable
|
NA Months
Median OS was not reached (only 15 of 47 evaluable subjects died)
|
SECONDARY outcome
Timeframe: Every 6 months while on treatment (estimated 4-10 months)Population: Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
To determine the proportion of subjects with clinical benefit (complete response, partial response, or stable disease) based on RECIST 1.1, where: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=13 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
n=46 Participants
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Clinical Benefit Rate
|
91.67 percentage of subjects
|
100 percentage of subjects
|
SECONDARY outcome
Timeframe: Every week while on treatment (estimated 4-10 months)Population: The analysis population for this objective was defined in the protocol as "all subjects who received at least one dose of study drug". No per-arm or per-cohort analyses were planned or performed.
Characterize adverse effects (AE) of pembrolizumab in combination with bevacizumab in subjects with metastatic RCC after failure of at least one systemic therapy. Toxicity will be assessed using CTCAE version 4. All grade 3 and 4 treatment-related adverse events will be reported.
Outcome measures
| Measure |
Arm A - Phase 1b Dose Escalation Cohort
n=60 Participants
Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
|
Arm B - Phase II Investigational Treatment
The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.
MK-3475: Arm B: Phase II Treatment: 200mg IV
Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.
|
|---|---|---|
|
Characterize Adverse Events
Diarrhea: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Arthralgia: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Alkaline phosphatase increased: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Duodenal ulcer: Grade 4
|
1 events
|
—
|
|
Characterize Adverse Events
Hyponatremia: Grade 4
|
1 events
|
—
|
|
Characterize Adverse Events
Hypertension: Grade 3
|
15 events
|
—
|
|
Characterize Adverse Events
Proteinuria: Grade 3
|
6 events
|
—
|
|
Characterize Adverse Events
Adrenal insufficiency: Grade 3
|
4 events
|
—
|
|
Characterize Adverse Events
Pain/Headaches: Grade 3
|
3 events
|
—
|
|
Characterize Adverse Events
Pneumonitis: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Hyponatremia: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Generalized muscle weakness: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Dehydration: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Skin Rashes: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Anemia: Grade 3
|
2 events
|
—
|
|
Characterize Adverse Events
Nausea: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Vomiting: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Thromboembolic event: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Seizure: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Myocardial infarction: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Mucositis oral: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Immune mediated hepatitis: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Immune mediated gastritis: Grade 3
|
1 events
|
—
|
|
Characterize Adverse Events
Hypothyroidism
|
1 events
|
—
|
|
Characterize Adverse Events
Hematuria
|
1 events
|
—
|
|
Characterize Adverse Events
Flu like symptoms: Grade 3
|
1 events
|
—
|
Adverse Events
All Subjects
Serious events: 32 serious events
Other events: 60 other events
Deaths: 28 deaths
Serious adverse events
| Measure |
All Subjects
n=61 participants at risk
Adverse events are summarized for all study participants who received at least one dose of study drug. Per the protocol, the safety analysis population "will comprise all subjects who received at least one dose of study drug". Consequently, no per-group analyses were planned or performed.
|
|---|---|
|
Infections and infestations
ABDOMINAL INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Blood and lymphatic system disorders
ANEMIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
ANOREXIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
BUTTOCK PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
CARDIAC DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
CHEST WALL PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
COLITIS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DUODENAL ULCER
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
GASTROINTESTINAL DISORDERS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
GENERALIZED MUSCLE WEAKNESS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
HEADACHE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
HEART FAILURE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
HEMATURIA
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERCALCEMIA
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERGLYCEMIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
HYPOTENSION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
HYPOTHYROIDISM
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
INFECTIONS AND INFESTATIONS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
MUSCLE WEAKNESS LOWER LIMB
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
PANCREATITIS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
PELVIC PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
PROTEINURIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
SEIZURE
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
SMALL INTESTINE INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
SOFT TISSUE INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
STROKE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
SYNCOPE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
TRANSIENT ISCHEMIC ATTACKS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
UPPER RESPIRATORY INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
VASCULAR DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
Other adverse events
| Measure |
All Subjects
n=61 participants at risk
Adverse events are summarized for all study participants who received at least one dose of study drug. Per the protocol, the safety analysis population "will comprise all subjects who received at least one dose of study drug". Consequently, no per-group analyses were planned or performed.
|
|---|---|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
16.4%
10/61 • Number of events 15 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
|
8.2%
5/61 • Number of events 6 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
ADRENAL INSUFFICIENCY
|
4.9%
3/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
ADULT RESPIRATORY DISTRESS SYNDROME
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
14.8%
9/61 • Number of events 15 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
ALKALINE PHOSPHATASE INCREASED
|
18.0%
11/61 • Number of events 16 • Every week while on treatment (estimated 4-10 months)
|
|
Immune system disorders
ALLERGIC REACTION
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
ANAL HEMORRHAGE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Blood and lymphatic system disorders
ANEMIA
|
19.7%
12/61 • Number of events 18 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
ANOREXIA
|
41.0%
25/61 • Number of events 35 • Every week while on treatment (estimated 4-10 months)
|
|
Psychiatric disorders
ANXIETY
|
9.8%
6/61 • Number of events 7 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
11.5%
7/61 • Number of events 10 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
16.4%
10/61 • Number of events 10 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
19.7%
12/61 • Number of events 17 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
ATAXIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
26.2%
16/61 • Number of events 21 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
BLOATING
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Blood and lymphatic system disorders
BLOOD AND LYMPHATIC SYSTEM DISORDERS
|
3.3%
2/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
8.2%
5/61 • Number of events 8 • Every week while on treatment (estimated 4-10 months)
|
|
Eye disorders
BLURRED VISION
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
BREAST PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
BRONCHIAL INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Injury, poisoning and procedural complications
BRUISING
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Injury, poisoning and procedural complications
BURN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
BUTTOCK PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
CARDIAC DISORDERS
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
CHEST PAIN - CARDIAC
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
CHILLS
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
CHOLESTEROL HIGH
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
COGNITIVE DISTURBANCE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
COLITIS
|
3.3%
2/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
CONSTIPATION
|
41.0%
25/61 • Number of events 34 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
41.0%
25/61 • Number of events 34 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
CREATININE INCREASED
|
34.4%
21/61 • Number of events 38 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
9.8%
6/61 • Number of events 9 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DENTAL CARIES
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Psychiatric disorders
DEPRESSION
|
9.8%
6/61 • Number of events 7 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DIARRHEA
|
41.0%
25/61 • Number of events 40 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
DIZZINESS
|
19.7%
12/61 • Number of events 15 • Every week while on treatment (estimated 4-10 months)
|
|
Eye disorders
DRY EYE
|
3.3%
2/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DRY MOUTH
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
16.4%
10/61 • Number of events 12 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
DYSGEUSIA
|
11.5%
7/61 • Number of events 7 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DYSPEPSIA
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
DYSPHAGIA
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
19.7%
12/61 • Number of events 17 • Every week while on treatment (estimated 4-10 months)
|
|
Ear and labyrinth disorders
EAR AND LABYRINTH DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Ear and labyrinth disorders
EAR PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
EDEMA FACE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
EDEMA LIMBS
|
31.1%
19/61 • Number of events 24 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
ENDOCRINE DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
16.4%
10/61 • Number of events 14 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
ERECTILE DYSFUNCTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA MULTIFORME
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Eye disorders
EYE DISORDERS
|
6.6%
4/61 • Number of events 6 • Every week while on treatment (estimated 4-10 months)
|
|
Eye disorders
EYE PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Injury, poisoning and procedural complications
FALL
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
FATIGUE
|
72.1%
44/61 • Number of events 66 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
FEVER
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
4.9%
3/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
FLATULENCE
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
FLU LIKE SYMPTOMS
|
4.9%
3/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Injury, poisoning and procedural complications
FRACTURE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
GASTRIC ULCER
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
GASTRITIS
|
6.6%
4/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
GASTROESOPHAGEAL REFLUX DISEASE
|
13.1%
8/61 • Number of events 9 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
GASTROINTESTINAL DISORDERS
|
21.3%
13/61 • Number of events 18 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
|
13.1%
8/61 • Number of events 15 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
GENERALIZED MUSCLE WEAKNESS
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
GENITAL EDEMA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
HEADACHE
|
41.0%
25/61 • Number of events 34 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
HEMATURIA
|
14.8%
9/61 • Number of events 13 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
HEMOGLOBIN INCREASED
|
3.3%
2/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
HEMORRHOIDAL HEMORRHAGE
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
HEMORRHOIDS
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Hepatobiliary disorders
HEPATOBILIARY DISORDERS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
HICCUPS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
HOARSENESS
|
13.1%
8/61 • Number of events 8 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
HOT FLASHES
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERCALCEMIA
|
16.4%
10/61 • Number of events 13 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERGLYCEMIA
|
18.0%
11/61 • Number of events 22 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERKALEMIA
|
24.6%
15/61 • Number of events 19 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPERNATREMIA
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
HYPERPARATHYROIDISM
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
HYPERTENSION
|
63.9%
39/61 • Number of events 93 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
HYPERTHYROIDISM
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPOALBUMINEMIA
|
13.1%
8/61 • Number of events 10 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPOCALCEMIA
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPOGLYCEMIA
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPOKALEMIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPOMAGNESEMIA
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
HYPONATREMIA
|
18.0%
11/61 • Number of events 27 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
HYPOTENSION
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Endocrine disorders
HYPOTHYROIDISM
|
23.0%
14/61 • Number of events 16 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
INFECTIONS AND INFESTATIONS
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Injury, poisoning and procedural complications
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
INR INCREASED
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Psychiatric disorders
INSOMNIA
|
19.7%
12/61 • Number of events 14 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
INVESTIGATIONS
|
16.4%
10/61 • Number of events 20 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
IRRITABILITY
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
LEFT VENTRICULAR SYSTOLIC DYSFUNCTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
4.9%
3/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
LIP INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
LIPASE INCREASED
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
LOCALIZED EDEMA
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
LOWER GASTROINTESTINAL HEMORRHAGE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
LUNG INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
LYMPHEDEMA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
LYMPHOCYTE COUNT DECREASED
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
MEMORY IMPAIRMENT
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Social circumstances
MENOPAUSE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Metabolism and nutrition disorders
METABOLISM AND NUTRITION DISORDERS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
MUCOSITIS ORAL
|
14.8%
9/61 • Number of events 14 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER
|
36.1%
22/61 • Number of events 29 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
11.5%
7/61 • Number of events 8 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
NAIL INFECTION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
NAIL RIDGING
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
NAUSEA
|
44.3%
27/61 • Number of events 38 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
NECK EDEMA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
NERVOUS SYSTEM DISORDERS
|
8.2%
5/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
ORAL DYSESTHESIA
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
ORAL PAIN
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
OSTEONECROSIS OF JAW
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
General disorders
PAIN
|
19.7%
12/61 • Number of events 14 • Every week while on treatment (estimated 4-10 months)
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
26.2%
16/61 • Number of events 28 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
PALPITATIONS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
PANCREATITIS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
PAPULOPUSTULAR RASH
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
PARESTHESIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
PERIORBITAL EDEMA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
PLATELET COUNT DECREASED
|
9.8%
6/61 • Number of events 9 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
6.6%
4/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
POSTNASAL DRIP
|
9.8%
6/61 • Number of events 8 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
11.5%
7/61 • Number of events 8 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
PROTEINURIA
|
39.3%
24/61 • Number of events 62 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
32.8%
20/61 • Number of events 24 • Every week while on treatment (estimated 4-10 months)
|
|
Psychiatric disorders
PSYCHIATRIC DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
PURPURA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
RASH ACNEIFORM
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
31.1%
19/61 • Number of events 27 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
RECTAL HEMORRHAGE
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
RENAL AND URINARY DISORDERS
|
16.4%
10/61 • Number of events 15 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
REPRODUCTIVE SYSTEM AND BREAST DISORDERS
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
|
21.3%
13/61 • Number of events 20 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
RHINITIS INFECTIVE
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
SEIZURE
|
3.3%
2/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
SERUM AMYLASE INCREASED
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
SINUS BRADYCARDIA
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
SINUS PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
SINUS TACHYCARDIA
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
SINUSITIS
|
11.5%
7/61 • Number of events 12 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
|
36.1%
22/61 • Number of events 32 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
SKIN HYPERPIGMENTATION
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
SKIN INFECTION
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Skin and subcutaneous tissue disorders
SKIN ULCERATION
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
SLEEP APNEA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
SNEEZING
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
SOFT TISSUE INFECTION
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
SORE THROAT
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
STOMACH PAIN
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Surgical and medical procedures
SURGICAL AND MEDICAL PROCEDURES
|
4.9%
3/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
TESTICULAR DISORDER
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Reproductive system and breast disorders
TESTICULAR PAIN
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
3.3%
2/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
TOOTH INFECTION
|
4.9%
3/61 • Number of events 5 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
TOOTHACHE
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Nervous system disorders
TREMOR
|
3.3%
2/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
UPPER RESPIRATORY INFECTION
|
24.6%
15/61 • Number of events 22 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
URINARY FREQUENCY
|
3.3%
2/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
URINARY INCONTINENCE
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
URINARY RETENTION
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Infections and infestations
URINARY TRACT INFECTION
|
13.1%
8/61 • Number of events 9 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
URINARY TRACT PAIN
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Renal and urinary disorders
URINARY URGENCY
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Vascular disorders
VASCULAR DISORDERS
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Ear and labyrinth disorders
VERTIGO
|
1.6%
1/61 • Number of events 1 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
VOICE ALTERATION
|
6.6%
4/61 • Number of events 4 • Every week while on treatment (estimated 4-10 months)
|
|
Gastrointestinal disorders
VOMITING
|
24.6%
15/61 • Number of events 27 • Every week while on treatment (estimated 4-10 months)
|
|
Eye disorders
WATERING EYES
|
4.9%
3/61 • Number of events 3 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
WEIGHT GAIN
|
13.1%
8/61 • Number of events 9 • Every week while on treatment (estimated 4-10 months)
|
|
Investigations
WEIGHT LOSS
|
29.5%
18/61 • Number of events 19 • Every week while on treatment (estimated 4-10 months)
|
|
Respiratory, thoracic and mediastinal disorders
WHEEZING
|
1.6%
1/61 • Number of events 2 • Every week while on treatment (estimated 4-10 months)
|
Additional Information
Clinicaltrials.gov Results Coordinator
Hoosier Cancer Research Network
Phone: 317-921-2050
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place