Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

July 1, 2013 updated by: National Cancer Institute (NCI)

Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer

This phase I clinical trial is studying the side effects and best dose of veliparib and gemcitabine hydrochloride when given with cisplatin in treating patients with advanced biliary, pancreatic, urothelial, or non-small cell lung 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 cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Veliparib may help cisplatin and gemcitabine hydrochloride work better by making tumor cells more sensitive to the drugs.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum-tolerated dose of veliparib (ABT-888) (days 1-12 of a 21-day schedule) in combination with cisplatin (day 3) and gemcitabine (days 3, 10) in patients with advanced, previously untreated carcinoma of the bile ducts, gallbladder or pancreas, non-small cell lung cancer, or transitional cell carcinoma of the bladder/urothelial tract.

SECONDARY OBJECTIVES:

I. Describe the dose-limiting toxicity (DLT) and other toxicities associated with veliparib in combination with cisplatin plus gemcitabine as assessed by CTCAE v4.0.

II. Determine the recommended phase 2 dose of veliparib (ABT-888) (RP2D) in combination with cisplatin plus gemcitabine.

III. Document anti-tumor activity of veliparib (ABT-888), cisplatin, and gemcitabine as assessed by RECIST 1.1.

IV. Determine the plasma pharmacokinetics of veliparib (ABT-888), cisplatin, and gemcitabine.

V. Determine the abundance of gemcitabine triphosphate in PBMCs following gemcitabine administration.

VI. Measure the abundance of DNA-platinum adducts in tumor tissue following cisplatin administration.

VII. Measure PARP enzymatic activity in PBMC and tumor tissue following study treatment.

VIII. Perform an exploratory correlation between abundance of BRCA and other proteins assessed by tumor immunohistochemistry and clinical response.

OUTLINE: This is a multicenter, dose-escalation study of veliparib and gemcitabine hydrochloride. Patients are stratified according to presence of suspected or known BRCA mutations (no vs yes).

Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.

After completion of study treatment, patients are followed up for 4 weeks.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed advanced biliary/pancreatic cancer, urothelial cancer, or non-small cell lung cancer that is metastatic or unresectable
  • Patients with known CNS metastases should be excluded from this clinical trial
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST/ALT ≤ 2.5 times institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min
  • QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation (≤ CTCAE v.4 grade 2)
  • Not pregnant or nursing
  • 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
  • Patients must be able to swallow pills and have no significant impairment in gastrointestinal absorption

  • Patients with known or suspected germline mutation in BRCA1 or BRCA2 are eligible to participate

    • Patients in study screening (primarily those with pancreatic cancer) who have a family history that is suspicious for BRCA1 or BRCA2 germline mutation should be assessed by the BRCAPRO computer program to quantitate the likelihood of harboring a deleterious BRCA mutation
    • Patients found to have a BRCAPRO probability score of ≥ 20% should undergo formal full-sequence BRCA testing
    • Patients in screening with a BRCAPRO probability of ≥ 20% who decline genetic testing are not eligible to participate in this trial due to the potential to confound safety assessment

  • No uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • HIV-positive patients are eligible
  • No active seizure or history of seizure disorder
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib (ABT-888) or other agents used in this study
  • No peripheral neuropathy greater than grade1
  • No prior systemic treatment
  • No prior cytotoxic chemotherapy (neoadjuvant, adjuvant, or metastatic setting)
  • At least 4 weeks since major surgery or radiation therapy
  • Patients may not be receiving any other investigational agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (veliparib, gemcitabine hydrochloride, cisplatin)
Patients receive veliparib orally every 12 hours on days 1-12, gemcitabine hydrochloride IV over 30 minutes on days 3 and 10, and cisplatin IV over 60-120 minutes on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with suspected or known germline BRCA mutations may continue to receive single-agent veliparib continuously in the absence of disease progression or unacceptable toxicity. Patients may undergo blood, tumor tissue, and hair follicle sample collection periodically for pharmacokinetic and correlative studies.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • gemcitabine
  • dFdC
  • difluorodeoxycytidine hydrochloride
Drug: cisplatin
Given IV
Other Names:
  • CDDP
  • DDP
  • CACP
  • CPDD
Other: diagnostic laboratory biomarker analysis
Correlative studies
Drug: veliparib
Given orally
Other Names:
  • ABT-888

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine
Time Frame: 21 days
The maximum toxicity for each category of interest that are determined to be possibly, probably or definitely related to study treatment will be recorded for each patient and the summary results will be tabulated (according to CTCAE v4.0).
21 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose-limiting and other toxicities according to CTCAE v4.0
Time Frame: Up to 4 weeks post-treatment
Up to 4 weeks post-treatment
Recommended phase II dose
Time Frame: Up to 4 weeks post-treatment
Up to 4 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Leonard Appleman, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

January 22, 2011

First Submitted That Met QC Criteria

January 22, 2011

First Posted (Estimate)

January 25, 2011

Study Record Updates

Last Update Posted (Estimate)

July 2, 2013

Last Update Submitted That Met QC Criteria

July 1, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2011-02576
  • U01CA099168 (U.S. NIH Grant/Contract)
  • UPCI 10-037
  • CDR0000693751
  • PCI-10-037

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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