Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
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| ClinicalTrials.gov Identifier: NCT01585805 |
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Recruitment Status :
Active, not recruiting
First Posted : April 26, 2012
Last Update Posted : February 16, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Locally Advanced Pancreatic Adenocarcinoma Metastatic Pancreatic Adenocarcinoma Recurrent Pancreatic Carcinoma Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7 | Procedure: Biopsy Drug: Cisplatin Drug: Gemcitabine Drug: Gemcitabine Hydrochloride Drug: Veliparib | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 107 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | April 18, 2012 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Pancreatic Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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Procedure: Biopsy
Undergo biopsy
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Gemcitabine Given IV
Other Names:
Drug: Gemcitabine Hydrochloride Given IV
Other Names:
Drug: Veliparib Given PO
Other Names:
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Active Comparator: 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.
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Procedure: Biopsy
Undergo biopsy
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Gemcitabine Given IV
Other Names:
Drug: Gemcitabine Hydrochloride Given IV
Other Names:
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Experimental: 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.
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Drug: Veliparib
Given PO
Other Names:
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Primary Outcome Measures :
- Optimal dose of veliparib with gemcitabine hydrochloride and cisplatin (non-randomized part I) [ Time Frame: 21 days ]
- 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.
- 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.
Secondary Outcome Measures :
- 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 ]Kaplan-Meier method will be used.
- Incidence of adverse events (Parts I and II) [ Time Frame: Up to 5 years ]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.
- Disease control rate (complete response + partial response + stable disease) and duration of response (Parts I and II) [ Time Frame: Up to 5 years ]The disease control rate will be recorded for all three study arms.
- 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 ]Kaplan-Meier method will be used.
Other Outcome Measures:
- Molecular and genetic phenotype of tumors [ Time Frame: Up to day 84 ]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.
- Proportion of genetic reversions of BRCA gene mutations [ Time Frame: Up to day 84 ]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.
- Change in PAR levels [ Time Frame: Baseline up to day 84 ]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.
- Transcriptome analyses [ Time Frame: Up to day 84 ]Will be assessed by ribonucleic acid (RNA) sequencing. Descriptive statistics will be employed to describe the observed effects.
- Differentially expressed genes found [ Time Frame: Up to day 84 ]Will be assessed by the limma package, and standard cut-offs. Descriptive statistics will be employed to describe the observed effects.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
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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)
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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
Exclusion Criteria:
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01585805
Locations
| United States, Illinois | |
| University of Chicago Comprehensive Cancer Center | |
| Chicago, Illinois, United States, 60637 | |
| Ingalls Memorial Hospital | |
| Harvey, Illinois, United States, 60426 | |
| United States, Michigan | |
| University of Michigan Comprehensive Cancer Center | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Missouri | |
| Mercy Hospital Saint Louis | |
| Saint Louis, Missouri, United States, 63141 | |
| United States, New Jersey | |
| Memorial Sloan Kettering Basking Ridge | |
| Basking Ridge, New Jersey, United States, 07920 | |
| United States, New York | |
| Memorial Sloan Kettering Commack | |
| Commack, New York, United States, 11725 | |
| Memorial Sloan Kettering Westchester | |
| Harrison, New York, United States, 10604 | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Memorial Sloan Kettering Nassau | |
| Uniondale, New York, United States, 11553 | |
| Canada, Ontario | |
| University Health Network-Princess Margaret Hospital | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Israel | |
| Shaare Zedek Medical Center | |
| Jerusalem, Israel, 91031 | |
| Chaim Sheba Medical Center | |
| Tel Hashomer, Israel, 52621 | |
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Eileen M O'Reilly | Memorial Sloan Kettering Cancer Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01585805 |
| Other Study ID Numbers: |
NCI-2012-00864 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 ) N01CM00071 ( U.S. NIH Grant/Contract ) P30CA008748 ( U.S. NIH Grant/Contract ) U01CA069856 ( U.S. NIH Grant/Contract ) UM1CA186705 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 26, 2012 Key Record Dates |
| Last Update Posted: | February 16, 2023 |
| Last Verified: | February 2023 |
Additional relevant MeSH terms:
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Adenocarcinoma Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine |
Cisplatin Veliparib Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Poly(ADP-ribose) Polymerase Inhibitors |