Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
A Randomized Phase II Study of Gemcitabine, Cisplatin +/- Veliparib in Patients With Pancreas Adenocarcinoma and a Known BRCA/ PALB2 Mutation (Part I) and a Phase II Single Arm Study of Single-Agent Veliparib in Previously Treated Pancreas Adenocarcinoma (Part II)
10 other identifiers
interventional
88
3 countries
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2012
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 25, 2012
CompletedFirst Posted
Study publicly available on registry
April 26, 2012
CompletedStudy Start
First participant enrolled
May 15, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 6, 2026
CompletedMarch 11, 2025
March 1, 2025
12.6 years
April 25, 2012
March 8, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Optimal dose of veliparib with gemcitabine hydrochloride and cisplatin (non-randomized part I)
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.
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.
Up to 5 years
Secondary Outcomes (4)
Progression-free survival (Parts I and II)
From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 years
Incidence of adverse events (Parts I and II)
Up to 5 years
Disease control rate (complete response + partial response + stable disease) and duration of response (Parts I and II)
Up to 5 years
Overall survival (Parts I and II)
From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years
Other Outcomes (5)
Molecular and genetic phenotype of tumors
Up to day 84
Proportion of genetic reversions of BRCA gene mutations
Up to day 84
Change in PAR levels
Baseline up to day 84
- +2 more other outcomes
Study Arms (3)
Arm A (veliparib, gemcitabine hydrochloride, cisplatin)
EXPERIMENTALPatients 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 COMPARATORPatients 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)
EXPERIMENTALPatients 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.
Interventions
Undergo biopsy
Undergo tumor tissue and blood sample collection
Given IV
Undergo CT
Given IV
Given IV
Undergo MRI
Given PO
Eligibility Criteria
You may qualify if:
- 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, non-randomized, lead-in portion, patients with a known BRCA 1 or 2 or PALB2 mutation are eligible along with patients who potentially may have a likelihood of having a BRCA mutation (e.g., personal or family history of breast, pancreas, ovary, endometrial, prostate or other likely related malignancy)
- For part I, randomized portion, a known BRCA 1 or 2 or PALB2 mutation is required
- 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:
- For part I (arm A, B): 0-1 (Karnofsky \> 70%)
- For part II (arm C): 0-2 (Karnofsky \>= 60%)
- 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)
- +6 more criteria
You may not qualify if:
- 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
- For part I, prior adjuvant therapy with gemcitabine or a fluoropyrimidine therapy is permitted if completed \> 6 months prior to recurrence; no prior PARP inhibitor therapy is allowed
- For part II, no prior PARP inhibitor therapy is permitted and up to two prior treatment regimens are permitted as follows: 1 adjuvant and 1 metastatic; 1 locally advanced and 1 metastatic; or 2 metastatic, or a variation thereof
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
University of Michigan Comprehensive 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
Related Publications (1)
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.
PMID: 29223478DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eileen M O'Reilly
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 25, 2012
First Posted
April 26, 2012
Study Start
May 15, 2012
Primary Completion
December 31, 2024
Study Completion
March 6, 2026
Last Updated
March 11, 2025
Record last verified: 2025-03