Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer
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
V. Determine the abundance of gemcitabine triphosphate in PBMCs following gemcitabine
VI. Measure the abundance of DNA-platinum adducts in tumor tissue following cisplatin
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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).
University of Pittsburgh
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|