Locally Advanced Pancreatic AdenocarcinomaPhase 2NCT01585805
Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Locally Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by National Cancer Institute (NCI) at 12 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 15 May 2012to 9 Mar 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- Creatinine =< 1.5 x upper limit of normal (ULN) (measured within 14 days prior to administration of ABT-888)
- Measurable disease by RECIST criteria
- For the lead-in, non-randomized portion of part I, either measurable or evaluable disease is acceptable
- For part I, randomized portion, measurable disease is required
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
United States9 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Israel2 sites
Shaare Zedek Medical Center
Jerusalem, 91031
Chaim Sheba Medical Center
Tel HaShomer, 52621
Canada1 site
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: 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)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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:
- 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.
- Conditions
- Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8
- Being tested
- Biopsy Procedure, Biospecimen Collection, Cisplatin, Computed Tomography, Gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo tumor tissue and blood sample collection
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
GemcitabineDrug
Also called dFdC, dFdCyd, Difluorodeoxycytidine
Given IV
Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
VeliparibDrug
Also called ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Veliparib |
| 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging |
| 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Veliparib |
| 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. Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride; Drug: Veliparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years
Secondary outcomes (4)
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
Measured: From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 years
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.
Measured: 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.
Measured: Up to 5 years
Overall Survival (Parts I and II)
Kaplan-Meier method will be used.
Measured: From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2012 (estimated)
- Study start15 May 2012
- Primary completion31 Dec 2024
- Study completion9 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eileen M O'Reilly, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01585805
- Sponsor's protocol ID
- NCI-2012-00864
- Other IDs
- NCI-2012-00864, CDR0000732189, MSKCC-12-045, IRB#12-045, 8993, 8993, N01CM00032, N01CM00071
- Status last verified
- Sep 2026
- First submitted
- 25 Apr 2012
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 29223478
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01585805
- Acronym / sponsor ID
- NCI-2012-00864
- Conditions
- Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 83 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 May 2012 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 9 Mar 2027 (estimated)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Posted 19 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A (veliparib, gemcitabine hydrochloride, cisplatin) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Drug: Cisplatin, Procedure: Computed Tomography, Drug: Gemcitabine, Drug: Gemcitabine Hydrochloride, Procedure: Magnetic Resonance Imaging, Drug: VeliparibPatients 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 | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Drug: Cisplatin, Procedure: Computed Tomography, Drug: Gemcitabine, Drug: Gemcitabine Hydrochloride, Procedure: Magnetic Resonance ImagingPatients 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 | Procedure: Biospecimen Collection, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: VeliparibPatients 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. |
| Part I (veliparib, gemcitabine, cisplatin) | Experimental | Drug: Cisplatin, Drug: Gemcitabine, Drug: Gemcitabine Hydrochloride, Drug: VeliparibThere 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo tumor tissue and blood sample collection | Procedure or surgery | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Arm C (veliparib) |
| CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven IV | Drug | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Part I (veliparib, gemcitabine, cisplatin) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Arm C (veliparib) |
| GemcitabineAlso: dFdC, dFdCyd, DifluorodeoxycytidineGiven IV | Drug | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Part I (veliparib, gemcitabine, cisplatin) |
| Gemcitabine HydrochlorideAlso: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, GemzarGiven IV | Drug | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Part I (veliparib, gemcitabine, cisplatin) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm B (gemcitabine hydrochloride, cisplatin), Arm C (veliparib) |
| VeliparibAlso: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888Given PO | Drug | Arm A (veliparib, gemcitabine hydrochloride, cisplatin), Arm C (veliparib), Part I (veliparib, gemcitabine, cisplatin) |
Primary outcome
Optimal Dose of Veliparib With Gemcitabine Hydrochloride and Cisplatin (Non-randomized Part I)
Time frame: 21 days
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.
Response Rate to Gemcitabine Hydrochloride and Cisplatin With Versus Without Veliparib (Randomized Part I)
Time frame: Up to 5 years
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.
Response Rate of Single-agent Veliparib (Part II)
Time frame: Up to 5 years
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.
4 secondary outcomes
Progression-free Survival (Parts I and II)
Time frame: From the date of study enrollment to documentation of clear-cut progression of disease or last follow-up, assessed up to 5 years
Number of Participants With Adverse Events (Parts I and II)
Time frame: Up to 5 years
Disease Control Rate (Complete Response + Partial Response + Stable Disease) and Duration of Response (Parts I and II)
Time frame: Up to 5 years
Overall Survival (Parts I and II)
Time frame: From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29223478Lowery 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eileen M O'Reilly principal investigator
Memorial Sloan Kettering Cancer Center
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Locally Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by National Cancer Institute (NCI) at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Israel, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal Dose of Veliparib With Gemcitabine Hydrochloride and Cisplatin (Non-randomized Part I) (time frame: 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01585805, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.