Trial Outcomes & Findings for Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (NCT NCT01585805)
NCT ID: NCT01585805
Last Updated: 2026-05-19
Results Overview
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
83 participants
Primary outcome timeframe
21 days
Results posted on
2026-05-19
Participant Flow
Prior to randomization, some participants either withdrew consent or were excluded because of ineligibility. Two participants withdrew consent after they were randomized to Arm B.
Participant milestones
| Measure |
Part I Lead In: Veliparib 20mg
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 40mg
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 80mg
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 80mg Cont
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
6
|
5
|
27
|
23
|
16
|
|
Overall Study
COMPLETED
|
3
|
3
|
6
|
5
|
27
|
23
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Part I Lead In: Veliparib 20mg
n=3 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 40mg
n=3 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 80mg
n=6 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lead In: Veliparib 80mg Cont
n=5 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Total
n=83 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
66 years
n=30 Participants
|
60 years
n=30 Participants
|
55.5 years
n=60 Participants
|
68 years
n=133 Participants
|
64 years
n=21 Participants
|
63 years
n=105 Participants
|
52 years
n=99 Participants
|
62 years
n=48 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
4 Participants
n=60 Participants
|
3 Participants
n=133 Participants
|
12 Participants
n=21 Participants
|
10 Participants
n=105 Participants
|
8 Participants
n=99 Participants
|
37 Participants
n=48 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=30 Participants
|
3 Participants
n=30 Participants
|
2 Participants
n=60 Participants
|
2 Participants
n=133 Participants
|
15 Participants
n=21 Participants
|
13 Participants
n=105 Participants
|
8 Participants
n=99 Participants
|
46 Participants
n=48 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
2 Participants
n=48 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=30 Participants
|
3 Participants
n=30 Participants
|
6 Participants
n=60 Participants
|
5 Participants
n=133 Participants
|
27 Participants
n=21 Participants
|
21 Participants
n=105 Participants
|
16 Participants
n=99 Participants
|
81 Participants
n=48 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
0 Participants
n=48 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
0 Participants
n=48 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=105 Participants
|
1 Participants
n=99 Participants
|
2 Participants
n=48 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
0 Participants
n=48 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=60 Participants
|
2 Participants
n=133 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
5 Participants
n=48 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=30 Participants
|
3 Participants
n=30 Participants
|
5 Participants
n=60 Participants
|
3 Participants
n=133 Participants
|
25 Participants
n=21 Participants
|
21 Participants
n=105 Participants
|
14 Participants
n=99 Participants
|
74 Participants
n=48 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=105 Participants
|
0 Participants
n=99 Participants
|
0 Participants
n=48 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=133 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=105 Participants
|
1 Participants
n=99 Participants
|
2 Participants
n=48 Participants
|
|
Region of Enrollment
Canada
|
0 participants
n=30 Participants
|
0 participants
n=30 Participants
|
1 participants
n=60 Participants
|
0 participants
n=133 Participants
|
1 participants
n=21 Participants
|
0 participants
n=105 Participants
|
3 participants
n=99 Participants
|
5 participants
n=48 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=30 Participants
|
3 participants
n=30 Participants
|
5 participants
n=60 Participants
|
5 participants
n=133 Participants
|
22 participants
n=21 Participants
|
20 participants
n=105 Participants
|
9 participants
n=99 Participants
|
67 participants
n=48 Participants
|
|
Region of Enrollment
Israel
|
0 participants
n=30 Participants
|
0 participants
n=30 Participants
|
0 participants
n=60 Participants
|
0 participants
n=133 Participants
|
4 participants
n=21 Participants
|
3 participants
n=105 Participants
|
4 participants
n=99 Participants
|
11 participants
n=48 Participants
|
PRIMARY outcome
Timeframe: 21 daysPopulation: Only applicable to participants in Part I Lead In Cohorts. Data is reported as per study design and as published. Pre-specified in the study protocol to collect, analyze, and report as a single Arm/Group
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib.
Outcome measures
| Measure |
Part I Lead In
n=17 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Optimal Dose of Veliparib With Gemcitabine Hydrochloride and Cisplatin (Non-randomized Part I)
|
80 mg
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 5 yearsPopulation: Applicable to participants in Arm A and Arm B
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Simon's two-stage minimax design will be employed separately in each arm A and B. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Part I Lead In
n=3 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=3 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=6 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=5 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Response Rate to Gemcitabine Hydrochloride and Cisplatin With Versus Without Veliparib (Randomized Part I)
Participants with Response Rate
|
1 Participants
|
1 Participants
|
4 Participants
|
1 Participants
|
—
|
20 Participants
|
15 Participants
|
|
Response Rate to Gemcitabine Hydrochloride and Cisplatin With Versus Without Veliparib (Randomized Part I)
Participants without Response Rate
|
2 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
—
|
7 Participants
|
8 Participants
|
PRIMARY outcome
Timeframe: Up to 5 yearsPopulation: Applicable to participants of Arm C
Will be assessed by RECIST criteria. Simon's two-stage optimal design will be employed. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Part I Lead In
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Response Rate of Single-agent Veliparib (Part II)
Stable disease
|
—
|
—
|
—
|
—
|
5 Participants
|
—
|
—
|
|
Response Rate of Single-agent Veliparib (Part II)
Progressive disease
|
—
|
—
|
—
|
—
|
11 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 yearsPopulation: For Part I of the study, the focus is primarily on evaluating pt safety and adjudicating the optimal dose of veliparib to cisplatin and gemcitabine. Combining the Part I pt data is appropriate as there are small numbers of pts and to evaluate them uncombined with regard to an efficacy signal would be an overinterpretation of the data. It was pre-specified in the study protocol to collect, analyze, and report Part I as a single Arm. Phase II portion of the study was designed to test efficacy.
Kaplan-Meier method will be used. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Part I Lead In
n=17 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Progression-free Survival (Parts I and II)
|
4.2 months
Interval 4.0 to 13.8
|
10.1 months
Interval 6.7 to 11.5
|
9.7 months
Interval 4.2 to 13.6
|
1.7 months
Interval 1.57 to 1.83
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsWill be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 will be utilized for adverse event reporting beginning April 1, 2018). Toxicity and tolerability of all three study arms will be assessed and summarized using descriptive statistics.
Outcome measures
| Measure |
Part I Lead In
n=3 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=3 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=6 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=5 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (Parts I and II)
|
3 Participants
|
3 Participants
|
6 Participants
|
5 Participants
|
16 Participants
|
27 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsThe disease control rate will be recorded for all three study arms.
Outcome measures
| Measure |
Part I Lead In
n=3 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=3 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=6 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=5 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Disease Control Rate (Complete Response + Partial Response + Stable Disease) and Duration of Response (Parts I and II)
Disease control rate (complete response + partial response + stable disease)
|
3 Participants
|
3 Participants
|
5 Participants
|
5 Participants
|
5 Participants
|
27 Participants
|
18 Participants
|
|
Disease Control Rate (Complete Response + Partial Response + Stable Disease) and Duration of Response (Parts I and II)
Progressive Disease
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
11 Participants
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: From the time of study enrollment to the date of death or last follow-up, assessed up to 5 yearsPopulation: For Part I of the study, the focus is primarily on evaluating pt safety and adjudicating the optimal dose of veliparib to cisplatin and gemcitabine. Combining the Part I pt data is appropriate as there are small numbers of pts and to evaluate them uncombined with regard to an efficacy signal would be an overinterpretation of the data. It was pre-specified in the study protocol to collect, analyze, and report Part I as a single Arm. Phase II portion of the study was designed to test efficacy.
Kaplan-Meier method will be used.
Outcome measures
| Measure |
Part I Lead In
n=9 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=8 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=23 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=16 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Overall Survival (Parts I and II)
|
23.3 months
Interval 3.8 to 30.2
|
11 months
Interval 1.5 to 12.1
|
15.5 months
Interval 12.2 to 24.3
|
16.4 months
Interval 11.7 to 23.4
|
—
|
3.1 months
Interval 1.9 to 4.1
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to day 84Population: BRCA confirmation was not a requirement for lead in Part I participants. BRCA confirmation was a requirement for Arm A, B and C participants; so 100% of participants in the randomized part of the trial and in the single arm phase II of veliparib had genomic testing completed. It was pre-specified in the study protocol to collect, analyze, and report Part I as a single Arm/Group.
Descriptive statistics will be utilized. An exploratory analysis will be undertaken to correlate the molecular profiling with outcome (e.g., response, progression-free survival time, overall survival time). Kaplan-Meier plots and Cox regression will be used for exploratory analysis of the survival endpoints and logistic regression will be used for response endpoints.
Outcome measures
| Measure |
Part I Lead In
n=17 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Molecular and Genetic Phenotype of Tumors
BRCA +
|
9 Participants
|
26 Participants
|
21 Participants
|
16 Participants
|
—
|
—
|
—
|
|
Molecular and Genetic Phenotype of Tumors
BRCA -
|
7 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Molecular and Genetic Phenotype of Tumors
Unknown
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Molecular and Genetic Phenotype of Tumors
PALB2 +
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to day 84Population: BRCA confirmation was not a requirement for lead in Part I participants. BRCA confirmation was a requirement for Arm A, B and C participants; so 100% of participants in the randomized part of the trial and in the single arm phase II of veliparib had genomic testing completed. It was pre-specified in the study protocol to collect, analyze, and report Part I as a single Arm/Group.
The evaluation will be a descriptive and exploratory one. The proportion of genetic reversions of BRCA gene mutations to wild type will be summarized using binomial proportions.
Outcome measures
| Measure |
Part I Lead In
n=17 Participants
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 Participants
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 Participants
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 Participants
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm C (Veliparib)
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
|---|---|---|---|---|---|---|---|
|
Proportion of Genetic Reversions of BRCA Gene Mutations
BRCA +
|
53 Percentage of participants
|
100 Percentage of participants
|
100 Percentage of participants
|
100 Percentage of participants
|
—
|
—
|
—
|
|
Proportion of Genetic Reversions of BRCA Gene Mutations
BRCA -
|
41 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
—
|
|
Proportion of Genetic Reversions of BRCA Gene Mutations
Undefined
|
6 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to day 84Population: Study resources were prioritized for primary and secondary outcome measures.
Summarized by percent of baseline. In each arm, a paired t-test will be employed to compare baseline to after treatment PAR levels. Standard descriptive methods will be used to summarize baseline levels and the changes from baseline (following treatment). Changes in PAR levels from baseline to after treatment will be associated with response using Wilcoxon rank sum test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to day 84Population: Study resources were prioritized for primary and secondary outcome measures.
Will be assessed by ribonucleic acid (RNA) sequencing. Descriptive statistics will be employed to describe the observed effects.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to day 84Population: Study resources were prioritized for primary and secondary outcome measures.
Will be assessed by the limma package, and standard cut-offs. Descriptive statistics will be employed to describe the observed effects.
Outcome measures
Outcome data not reported
Adverse Events
Part I Lean In: Veliparib 20 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Part I Lean In: Veliparib 40 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Part I Lean In: Veliparib 80 mg
Serious events: 4 serious events
Other events: 6 other events
Deaths: 6 deaths
Part I Lean In: Veliparib 80 mg Cont
Serious events: 3 serious events
Other events: 5 other events
Deaths: 3 deaths
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
Serious events: 10 serious events
Other events: 27 other events
Deaths: 20 deaths
Arm B (Gemcitabine Hydrochloride, Cisplatin)
Serious events: 5 serious events
Other events: 19 other events
Deaths: 21 deaths
Arm C (Veliparib)
Serious events: 8 serious events
Other events: 10 other events
Deaths: 14 deaths
Serious adverse events
| Measure |
Part I Lean In: Veliparib 20 mg
n=3 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 40 mg
n=3 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 80 mg
n=6 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 80 mg Cont
n=5 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 participants at risk
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 participants at risk
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 participants at risk
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Skin infection
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Leukemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
4.3%
1/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
2/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
4.3%
1/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
AST
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
ALT
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
General disorders
Fever
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
4.3%
1/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
General disorders
Fatigue
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
2/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Colon Perforation
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Infections and infestations
Biliary tract infection
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Nervous system disorders
Seizure
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
33.3%
1/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
General disorders
Edema limbs
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
General disorders
Edema trunk
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Colonic Obstruction
|
0.00%
0/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Ileus
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Infections and infestations
Lung infection
|
33.3%
1/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
Other adverse events
| Measure |
Part I Lean In: Veliparib 20 mg
n=3 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 40 mg
n=3 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 80 mg
n=6 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Part I Lean In: Veliparib 80 mg Cont
n=5 participants at risk
There will be a small lead-in, non-randomized portion to Part I, where dose levels of veliparib 20 mg po BID (dose level 0), 40 mg po BID (dose level 1) and 80 mg po BID (dose level 2), will be evaluated on a day 1-12 schedule. The doses of gemcitabine 600 mg/m2 and cisplatin 25 mg/m2 are fixed. Three-6 patients will be evaluated per dose level starting with 20 mg po BID (dose level 0). If no dose-limiting toxicity (DLT), the dose of veliparib will be increased to 40 mg po BID (dose level 1) and subsequently to 80 mg po BID (dose level 2). If no DLT is observed at the veliparib dose of 80 mg BID day 1-12, then dose level 2A will examine veliparib at 80 mg po BID day 1-21, i.e., continuous dosing of veliparib. Subsequent cohorts will only examine continuous dosing of veliparib: dose level 3 (140mg po BID) and dose level 4 (200mg po BID). Approximately 6-24 patients total will be evaluated in this lead in portion of the study
|
Arm A (Veliparib, Gemcitabine Hydrochloride, Cisplatin)
n=27 participants at risk
Patients receive veliparib PO BID on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
Arm B (Gemcitabine Hydrochloride, Cisplatin)
n=23 participants at risk
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
Biopsy: Undergo biopsy
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Cisplatin: Given IV
Computed Tomography: Undergo CT
Gemcitabine: Given IV
Gemcitabine Hydrochloride: Given IV
Magnetic Resonance Imaging: Undergo MRI
|
Arm C (Veliparib)
n=16 participants at risk
Patients receive veliparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial.
Biospecimen Collection: Undergo tumor tissue and blood sample collection
Computed Tomography: Undergo CT
Magnetic Resonance Imaging: Undergo MRI
Veliparib: Given PO
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Biliary Infections
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Infections and infestations
Infections (other)
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
14.8%
4/27 • Up to 5 years
|
4.3%
1/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Colon Perforation
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Vascular disorders
Hypertension
|
66.7%
2/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
21.7%
5/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
18.5%
5/27 • Up to 5 years
|
26.1%
6/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
GI bleeding
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
17.4%
4/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
2/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
11.1%
3/27 • Up to 5 years
|
13.0%
3/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Increased alkaline phosphatase
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
33.3%
9/27 • Up to 5 years
|
21.7%
5/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
11.1%
3/27 • Up to 5 years
|
4.3%
1/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Vascular disorders
Deep venous thrombosis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
18.5%
5/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Vascular disorders
Pulmonary embolus
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Weight loss
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
66.7%
2/3 • Up to 5 years
|
66.7%
2/3 • Up to 5 years
|
83.3%
5/6 • Up to 5 years
|
60.0%
3/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
50.0%
3/6 • Up to 5 years
|
40.0%
2/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
33.3%
1/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
33.3%
2/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
14.8%
4/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Alkaline-Phosphate
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Investigations
AST
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
11.1%
3/27 • Up to 5 years
|
21.7%
5/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Investigations
ALT
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
14.8%
4/27 • Up to 5 years
|
34.8%
8/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Creatinine
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
3.7%
1/27 • Up to 5 years
|
34.8%
8/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
General disorders
Fatigue
|
33.3%
1/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
16.7%
1/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
37.0%
10/27 • Up to 5 years
|
34.8%
8/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
18.5%
5/27 • Up to 5 years
|
21.7%
5/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
25.9%
7/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
100.0%
3/3 • Up to 5 years
|
33.3%
1/3 • Up to 5 years
|
33.3%
2/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
40.7%
11/27 • Up to 5 years
|
47.8%
11/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
50.0%
3/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
7.4%
2/27 • Up to 5 years
|
17.4%
4/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Leukopenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
70.4%
19/27 • Up to 5 years
|
69.6%
16/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Investigations
Neutropenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
20.0%
1/5 • Up to 5 years
|
0.00%
0/27 • Up to 5 years
|
0.00%
0/23 • Up to 5 years
|
0.00%
0/16 • Up to 5 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
22.2%
6/27 • Up to 5 years
|
26.1%
6/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
81.5%
22/27 • Up to 5 years
|
82.6%
19/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
85.2%
23/27 • Up to 5 years
|
69.6%
16/23 • Up to 5 years
|
12.5%
2/16 • Up to 5 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/3 • Up to 5 years
|
0.00%
0/6 • Up to 5 years
|
0.00%
0/5 • Up to 5 years
|
14.8%
4/27 • Up to 5 years
|
8.7%
2/23 • Up to 5 years
|
6.2%
1/16 • Up to 5 years
|
Additional Information
Dr. Eileen O'Reilly, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4182
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60