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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01282333
First received: January 22, 2011
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum-tolerated dose of veliparib in combination with cisplatin and gemcitabine [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Dose-limiting and other toxicities according to CTCAE v4.0 [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Recommended phase II dose [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: January 2011
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: veliparib
Given orally
Other Name: ABT-888
Other: diagnostic laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01282333

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Leonard Appleman University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01282333     History of Changes
Other Study ID Numbers: NCI-2011-02576, UPCI 10-037, CDR0000693751, PCI-10-037, U01CA099168
Study First Received: January 22, 2011
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Transitional Cell
Liver Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Gallbladder Neoplasms
Bile Duct Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases

ClinicalTrials.gov processed this record on August 19, 2014