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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-00864 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000732189 | |||
| MSKCC-12-045 | |||
| IRB#12-045 | |||
| 8993 | Other Identifier | Memorial Sloan Kettering Cancer Center | |
| 8993 | Other Identifier | CTEP | |
| N01CM00032 | U.S. NIH Grant/Contract | View source | |
| N01CM00071 | U.S. NIH Grant/Contract | View source | |
| P30CA008748 | U.S. NIH Grant/Contract | View source | |
| U01CA069856 | U.S. NIH Grant/Contract | View source | |
| UM1CA186705 | U.S. NIH Grant/Contract | View source |
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This randomized phase II trial studies how well veliparib together with gemcitabine hydrochloride and cisplatin works compared to gemcitabine hydrochloride and cisplatin alone in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or spread from the primary site (place where it started) to other places in the body (metastatic). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving veliparib together with gemcitabine hydrochloride and cisplatin is an effective treatment for pancreatic cancer.
PRIMARY OBJECTIVES:
I. To optimize the dose of veliparib combined with fixed doses of gemcitabine hydrochloride (gemcitabine) and cisplatin in a (non-randomized, lead-in portion of Part I).
II. To evaluate the response rate (Response Evaluation Criteria in Solid Tumors [RECIST] criteria) of gemcitabine, cisplatin, and veliparib (Arm A) and gemcitabine, cisplatin (Arm B) in BRCA and PALB2 mutation carriers with advanced pancreas adenocarcinoma. (Part I) III. To evaluate the response rate (RECIST criteria) of single-agent veliparib (Arm C) in BRCA and PALB2 carriers with previously treated pancreas adenocarcinoma. (Part II)
SECONDARY OBJECTIVES:
I. To evaluate the progression-free survival in study Arm A and Arm B. (Part I) II. To describe the safety and tolerability of gemcitabine, cisplatin, and veliparib and gemcitabine and cisplatin in BRCA and PALB2 carriers with advanced pancreas adenocarcinoma. (Part I) III. To determine the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) and duration of response in study Arm A and Arm B. (Part I) IV. To evaluate overall survival in study Arm A and Arm B. (Part I) V. To evaluate progression-free survival for single-agent veliparib in BRCA and PALB2 mutation carriers with previously treated pancreas adenocarcinoma (Arm C). (Part II) VI. To describe the safety and tolerability of single-agent veliparib in BRCA and PALB2 mutation carriers with previously treated pancreas adenocarcinoma. (Part II) VII. To determine the disease control rate (CR + PR + SD) and duration of response in Arm C. (Part II) VIII. To evaluate overall survival in Arm C. (Part II)
CORRELATIVE SCIENCE OBJECTIVES:
I. To determine the genotype of BRCA1, BRCA2 and PALB2-mutated pancreas adenocarcinoma.
II. To assess pre and post therapy biopsies for novel or persistent genetic alterations in genes identified in aim I.
III. To quantify levels of PAR in peripheral blood mononuclear cells (PBMCs) and tumor tissues at sequential time points before and following therapy with veliparib.
IV. To quantify levels of gammaH2AX and RAD51 foci in PBMCs and tumor tissue (where available) at sequential time points to assess for formation of double-stranded deoxyribonucleic acid (DNA) breaks, stalled/collapsed replication forks and evaluate homologous recombination competence.
EXPLORATORY OBJECTIVES:
I. To correlate the results of genotyping with gene expression to provide functional information on mutations identified.
II. An exploratory assessment of differential expression of genes involved in DNA repair pathways pre and post treatment to identify candidate genes predictive of response or resistance to therapy for further study in preclinical models of disease.
OUTLINE: This is a dose-escalation study of veliparib followed by a randomized, open-label study.
Patients receive veliparib orally (PO) twice daily (BID) on days 1-12 or 1-21 of each cycle. Patients also receive gemcitabine hydrochloride intravenously (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. (CLOSED AS OF 12/13/13)
Part I Lead-in/Non Randomized Portion: 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: Once the maximum-tolerated dose of veliparib has been established, patients are randomized to 1 of 2 treatment arms.
ARM A (no prior therapy or >= 6 months since adjuvant therapy): Patients receive veliparib PO BID on days 1-12 of each cycle and 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 computed tomography (CT) or magnetic resonance imaging (MRI) throughout study. Patients also undergo tumor tissue and blood sample collection throughout the trial and undergo tumor biopsy during screening and on study.
ARM B (no prior therapy or >= 6 months since adjuvant therapy): 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.
PART II: Patients who are eligible receive treatment in Arm C.
ARM C (prior therapy): 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.
After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (veliparib, gemcitabine hydrochloride, cisplatin) | Experimental | 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. |
|
| Arm B (gemcitabine hydrochloride, cisplatin) | Active Comparator | 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. |
|
| Arm C (veliparib) | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biopsy Procedure | Procedure | Undergo biopsy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Optimal Dose of Veliparib With Gemcitabine Hydrochloride and Cisplatin (Non-randomized Part I) | 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. | 21 days |
| Response Rate to Gemcitabine Hydrochloride and Cisplatin With Versus Without Veliparib (Randomized Part I) | 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. | Up to 5 years |
| Response Rate of Single-agent Veliparib (Part II) | 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. | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (Parts I and II) | 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 | From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Molecular and Genetic Phenotype of Tumors | 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. |
Inclusion Criteria:
Male or female patients with cytologically or histologically confirmed locally advanced or metastatic pancreas adenocarcinoma with a BRCA1 or 2 or PALB2 mutation confirmed by report from Myriad Genetics (United States of America [USA]); reports from other molecular diagnostic companies can be used to confirm mutations as well; BRCA 1 or 2 or PALB2 mutation can be confirmed locally for all international sites
For part I (arms A, B): Patients can have either locally advanced or metastatic pancreas adenocarcinoma for which no prior therapy has been administered for either locally advanced or metastatic disease; prior adjuvant therapy is permissible if gemcitabine or a fluoropyrimidine was administered with or without radiation and if disease recurrence has been documented at least 6 months after completion of adjuvant therapy
For part II (arm C): Patients can have either locally advanced or metastatic pancreas adenocarcinoma; up to two prior treatment regimens are permissible (excluding a prior PARP inhibitor) for either localized or metastatic pancreas adenocarcinoma; prior combined chemotherapy and radiotherapy is permissible provided the patient has measurable disease outside the radiation port; prior therapy must have been completed at least 3 weeks prior to starting therapy
Age > 18 years. No dosing or adverse event data are currently available on the use of veliparib in patients < 18 years of age, therefore children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status:
Life expectancy of greater than 3 months
Absolute neutrophil count >= 1,500/mcL (measured within 14 days prior to administration of ABT-888)
Hemoglobin >= 9.0 g/dl (measured within 14 days prior to administration of ABT-888)
Platelets >= 100,000/mcL (measured within 14 days prior to administration of ABT-888)
Total bilirubin =< 2 x institutional upper limit of normal (measured within 14 days prior to administration of ABT-888)
Aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase(ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x institutional upper limit of normal unless there is evidence of liver metastases in which case the AST (SGOT)/ALT (SGPT) must be =< 5 x institutional upper limit of normal (measured within 14 days prior to administration of ABT-888)
Creatinine =< 1.5 x upper limit of normal (ULN) (measured within 14 days prior to administration of ABT-888)
Measurable disease by RECIST criteria
If a woman is of child-bearing potential a negative blood or urine pregnancy test is required; (the effects of veliparib on the developing human fetus are unknown; for this reason and because other therapeutic agents or modalities used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception [hormonal or barrier method of birth control; abstinence] prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately)
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
Patients may not be receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
For part I: patients with known contraindications to platinum agents are excluded
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because veliparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with veliparib, breastfeeding should be discontinued if the mother is treated with veliparib; these potential risks may also apply to other agents used in this study
Patients with a known active infection, e.g., hepatitis B virus or hepatitis C virus; human immunodeficiency virus (HIV)-positive patients who are otherwise well and who do not have evidence of significant immune compromise are eligible
Patients with active seizure or history of seizure are not eligible
Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases are to be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
Patients with prior malignancy successfully treated who are currently stable and on no active treatment are eligible
Patients who are unable to swallow pills/capsules are ineligible
Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS are ineligible
Patients with prior allogeneic bone marrow transplant or double umbilical cord blood transplantation are ineligible
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| Name | Affiliation | Role |
|---|---|---|
| Eileen M O'Reilly | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Comprehensive Cancer Center | Chicago | Illinois | 60637 | United States | ||
| Ingalls Memorial Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29223478 | Derived | Lowery MA, Kelsen DP, Capanu M, Smith SC, Lee JW, Stadler ZK, Moore MJ, Kindler HL, Golan T, Segal A, Maynard H, Hollywood E, Moynahan M, Salo-Mullen EE, Do RKG, Chen AP, Yu KH, Tang LH, O'Reilly EM. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018 Jan;89:19-26. doi: 10.1016/j.ejca.2017.11.004. Epub 2017 Dec 8. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 23, 2023 |
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| Part I (veliparib, gemcitabine, cisplatin) | Experimental | 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. |
|
| Biospecimen Collection | Procedure | Undergo tumor tissue and blood sample collection |
|
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| Cisplatin | Drug | Given IV |
|
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| Computed Tomography | Procedure | Undergo CT |
|
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| Gemcitabine | Drug | Given IV |
|
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| Gemcitabine Hydrochloride | Drug | Given IV |
|
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| Magnetic Resonance Imaging | Procedure | Undergo MRI |
|
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| Veliparib | Drug | Given PO |
|
|
| Number of Participants With Adverse Events (Parts I and II) | Will 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. | Up to 5 years |
| Disease Control Rate (Complete Response + Partial Response + Stable Disease) and Duration of Response (Parts I and II) | The disease control rate will be recorded for all three study arms. | Up to 5 years |
| Overall Survival (Parts I and II) | Kaplan-Meier method will be used. | From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years |
| Up to day 84 |
| Proportion of Genetic Reversions of BRCA Gene Mutations | 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. | Up to day 84 |
| Change in PAR Levels | 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. | Baseline up to day 84 |
| Transcriptome Analyses | Will be assessed by ribonucleic acid (RNA) sequencing. Descriptive statistics will be employed to describe the observed effects. | Up to day 84 |
| Differentially Expressed Genes Found | Will be assessed by the limma package, and standard cut-offs. Descriptive statistics will be employed to describe the observed effects. | Up to day 84 |
| Harvey |
| Illinois |
| 60426 |
| United States |
| University of Michigan Rogel Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Mercy Hospital Saint Louis | St Louis | Missouri | 63141 | United States |
| Memorial Sloan Kettering Basking Ridge | Basking Ridge | New Jersey | 07920 | United States |
| Memorial Sloan Kettering Commack | Commack | New York | 11725 | United States |
| Memorial Sloan Kettering Westchester | Harrison | New York | 10604 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Memorial Sloan Kettering Nassau | Uniondale | New York | 11553 | United States |
| University Health Network-Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Shaare Zedek Medical Center | Jerusalem | 91031 | Israel |
| Chaim Sheba Medical Center | Tel Litwinsky | 52621 | Israel |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
| FG006 | 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 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | 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 |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Optimal Dose of Veliparib With Gemcitabine Hydrochloride and Cisplatin (Non-randomized Part I) | 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. | 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 | Posted | Number | mg | 21 days |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | Response Rate to Gemcitabine Hydrochloride and Cisplatin With Versus Without Veliparib (Randomized Part I) | 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. | Applicable to participants in Arm A and Arm B | Posted | Count of Participants | Participants | Up to 5 years |
| |||||||||||||||||||||||||||||||||||||
| Primary | Response Rate of Single-agent Veliparib (Part II) | 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. | Applicable to participants of Arm C | Posted | Count of Participants | Participants | Up to 5 years |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (Parts I and II) | 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 | 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. | Posted | Median | 95% Confidence Interval | months | From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 years |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (Parts I and II) | Will 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. | Posted | Count of Participants | Participants | Up to 5 years |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Disease Control Rate (Complete Response + Partial Response + Stable Disease) and Duration of Response (Parts I and II) | The disease control rate will be recorded for all three study arms. | Posted | Count of Participants | Participants | Up to 5 years |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (Parts I and II) | Kaplan-Meier method will be used. | 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. | Posted | Median | 95% Confidence Interval | months | From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Molecular and Genetic Phenotype of Tumors | 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. | 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. | Posted | Count of Participants | Participants | Up to day 84 |
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Proportion of Genetic Reversions of BRCA Gene Mutations | 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. | 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. | Posted | Number | Percentage of participants | Up to day 84 |
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in PAR Levels | 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. | Study resources were prioritized for primary and secondary outcome measures. | Posted | Baseline up to day 84 |
| |||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Transcriptome Analyses | Will be assessed by ribonucleic acid (RNA) sequencing. Descriptive statistics will be employed to describe the observed effects. | Study resources were prioritized for primary and secondary outcome measures. | Posted | Up to day 84 |
| |||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Differentially Expressed Genes Found | Will be assessed by the limma package, and standard cut-offs. Descriptive statistics will be employed to describe the observed effects. | Study resources were prioritized for primary and secondary outcome measures. | Posted | Up to day 84 |
|
Up to 5 years
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part I Lean In: Veliparib 20 mg | 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 | 2 | 3 | 1 | 3 | 3 | 3 |
| EG001 | Part I Lean In: Veliparib 40 mg | 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 | 2 | 3 | 2 | 3 | 3 | 3 |
| EG002 | Part I Lean In: Veliparib 80 mg | 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 | 6 | 6 | 4 | 6 | 6 | 6 |
| EG003 | Part I Lean In: Veliparib 80 mg 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 | 3 | 5 | 3 | 5 | 5 | 5 |
| EG004 | 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 | 20 | 27 | 10 | 27 | 27 | 27 |
| EG005 | 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 | 21 | 23 | 5 | 23 | 19 | 23 |
| EG006 | 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 | 14 | 16 | 8 | 16 | 10 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Leukemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| AST | Investigations | Systematic Assessment |
| ||
| ALT | Investigations | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Colon Perforation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Biliary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
| ||
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Edema limbs | General disorders | Systematic Assessment |
| ||
| Edema trunk | General disorders | Systematic Assessment |
| ||
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
| ||
| Colonic Obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Ileus | Gastrointestinal disorders | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Skin infection | Infections and infestations | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Investigations | Systematic Assessment |
| ||
| Neutropenia | Investigations | Systematic Assessment |
| ||
| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Alkaline-Phosphate | Investigations | Systematic Assessment |
| ||
| AST | Investigations | Systematic Assessment |
| ||
| ALT | Investigations | Systematic Assessment |
| ||
| Creatinine | Investigations | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Neuropathy | Nervous system disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Biliary Infections | Infections and infestations | Systematic Assessment |
| ||
| Infections (other) | Infections and infestations | Systematic Assessment |
| ||
| Colon Perforation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| GI bleeding | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Increased alkaline phosphatase | Investigations | Systematic Assessment |
| ||
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
| ||
| Deep venous thrombosis | Vascular disorders | Systematic Assessment |
| ||
| Pulmonary embolus | Vascular disorders | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Weight loss | Investigations | Systematic Assessment |
| ||
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Eileen O'Reilly, MD | Memorial Sloan Kettering Cancer Center | 646-888-4182 | oreillye@mskcc.org |
| Dec 24, 2025 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: P8993_A18ConsentPart1(Untracked).pdf | Oct 23, 2023 | Dec 24, 2025 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: P8993_A18ConsentPart2(Untracked).pdf | Oct 23, 2023 | Dec 24, 2025 | ICF_002.pdf |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D002945 | Cisplatin |
| C044245 | 1,2-diaminocyclohexaneplatinum II citrate |
| D010984 | Platinum |
| D000093542 | Gemcitabine |
| D009682 | Magnetic Resonance Spectroscopy |
| C521013 | veliparib |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D028561 | Transition Elements |
| D008670 | Metals |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Israel |
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| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
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| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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| OG001 | Part I: BRCA- | 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
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| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
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| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
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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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | 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 |
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