Veliparib, Cisplatin, And Gemcitabine Hydrochloride In Treating Patients With Advanced Biliary, Pancreatic, Urothelial, Or Non-Small Cell Lung Cancer

Study Overview

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or 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.

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.

Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Stage III Bladder Cancer
Stage III Pancreatic Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Bladder Cancer
Stage IV Non-small Cell Lung Cancer
Stage IV Pancreatic Cancer
Transitional Cell Carcinoma of the Bladder
Unresectable Extrahepatic Bile Duct Cancer
Unresectable Gallbladder Cancer

DRUG: gemcitabine hydrochloride
DRUG: veliparib
OTHER: diagnostic laboratory biomarker analysis
OTHER: pharmacological study
DRUG: cisplatin

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

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-01-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-07-01
First Submitted that Met QC Criteria 2011-01-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-07-02
First Posted (ESTIMATED) 2011-01-25	Results First Posted N/A	Last Verified 2013-07

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

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	DRUG: gemcitabine hydrochloride Given IV DRUG: veliparib Given orally OTHER: diagnostic laboratory biomarker analysis Correlative studies OTHER: pharmacological study Correlative studies DRUG: cisplatin Given IV

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

DRUG: gemcitabine hydrochloride

Given IV

DRUG: veliparib

Given orally

OTHER: diagnostic laboratory biomarker analysis

Correlative studies

OTHER: pharmacological study

Correlative studies

DRUG: cisplatin

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine	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	Measure Description	Time Frame
Dose-limiting and other toxicities according to CTCAE v4.0		Up to 4 weeks post-treatment
Recommended phase II dose		Up to 4 weeks post-treatment

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Leonard Appleman, University of Pittsburgh

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record