Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer
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
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|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|
- 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).
- 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 ]
|Study Start Date:||January 2011|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
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
Other Names:Drug: veliparib
Other Name: ABT-888Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: cisplatin
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.
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).
After completion of study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01282333
|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|
|Principal Investigator:||Leonard Appleman||University of Pittsburgh|