Trial record 1 of 1 for:    NCT01585805
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Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Patients With Locally Advanced or Metastatic Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01585805
First received: April 25, 2012
Last updated: September 23, 2014
Last verified: June 2014
  Purpose

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 locally advanced or metastatic pancreatic cancer. 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 or by stopping them from dividing. It is not yet known whether giving veliparib together with gemcitabine hydrochloride and cisplatin is an effective treatment for pancreatic cancer.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: veliparib
Drug: gemcitabine hydrochloride
Drug: cisplatin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Optimal dose of veliparib with gemcitabine hydrochloride and cisplatin (non-randomized part I) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Response rate to gemcitabine hydrochloride and cisplatin with versus without veliparib as assessed by RECIST (randomized Part I) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Simon's two-stage minimax design will be employed .

  • Response rate of single-agent veliparib using RECIST criteria (Part II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Simon's two-stage optimal design will be employed.


Secondary Outcome Measures:
  • Progression-free survival [ 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 ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicity and tolerability of all three study arms will be assessed and summarized using descriptive statistics.

  • Disease control rate (CR + PR + SD) and duration of response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the time of study enrollment to the date of death or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.


Other Outcome Measures:
  • Molecular and genetic phenotype of tumors [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Summarized by percent of baseline. In each arm, a paired t-test will be employed to compared 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 by ribonucleic acid (RNA) sequencing [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]
    Descriptive statistics will be employed to describe the observed effects.

  • Differentially expressed genes found using the limma package, and standard cut-offs [ Time Frame: Up to day 84 ] [ Designated as safety issue: No ]
    Descriptive statistics will be employed to describe the observed effects.


Estimated Enrollment: 107
Study Start Date: April 2012
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (veliparib, gemcitabine hydrochloride, cisplatin)
Patients receive veliparib PO BID on days 1-12 or 1-21. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 30 minutes on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm B (gemcitabine hydrochloride, cisplatin)
Patients receive gemcitabine hydrochloride IV and cisplatin IV as patients in arm A. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm C (veliparib)
Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 (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 study therapy
  • 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
  • Hemoglobin >= 9.0 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 2 times institutional upper limit of normal (ULN)
  • Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) =< 2.5 x institutional ULN unless there is evidence of liver metastases in which case the AST (SGOT)/ALT (SGPT) must be =< 5 times institutional ULN
  • Creatinine =< 1.5 x ULN
  • 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 serum or urine pregnancy test is required; 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

    • 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; 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; breastfeeding should be discontinued if the mother is treated with veliparib; this may also apply to other agents used in this study
  • Patients with an 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585805

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mary F. Mulcahy    312-695-4440    m-mulcahy@northwestern.edu   
Principal Investigator: Mary F. Mulcahy         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Hedy L. Kindler    773-702-0360    hkindler@medicine.bsd.uchicago.edu   
Principal Investigator: Hedy L. Kindler         
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Mark F. Kozloff    708-339-4800    mkozloff@bsd.uchicago.edu   
Principal Investigator: Mark F. Kozloff         
United States, Maryland
University of Maryland/Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Yixing Jiang    410-328-7225    yjiang@umm.edu   
Principal Investigator: Yixing Jiang         
United States, Michigan
University of Michigan University Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mark M. Zalupski    734-615-3969    zalupski@umich.edu   
Principal Investigator: Mark M. Zalupski         
United States, Missouri
Saint John's Mercy Medical Center Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Bethany G. Sleckman    314-251-7057    slecbg@stlo.mercy.net   
Principal Investigator: Bethany G. Sleckman         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eileen M. O'Reilly    646-888-4182    oreillye@mskcc.org   
Principal Investigator: Eileen M. O'Reilly         
Canada, Ontario
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Malcolm J. Moore    416-946-2263    Malcolm.moore@uhn.on.ca   
Principal Investigator: Malcolm J. Moore         
Israel
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, 91031
Contact: Amiel Segal    972-2-666-6331    segal@szmc.org.il   
Principal Investigator: Amiel Segal         
Chaim Sheba Medical Center Recruiting
Tel Hashomer, Israel, 52621
Contact: Talia Golan    972-3-530-3030    tailia.golan@sheba.health.gov.il   
Principal Investigator: Talia Golan         
Sponsors and Collaborators
Investigators
Principal Investigator: Eileen O'Reilly Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01585805     History of Changes
Other Study ID Numbers: NCI-2012-00864, NCI-2012-00864, CDR0000732189, MSKCC-12-045, 12-045, 8993, N01CM00032, N01CM00071, P30CA008748, U01CA069856
Study First Received: April 25, 2012
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014