Clinical Trial: Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: A Phase I Study of ABT-888 in Combination With Oxaliplatin and Capecitabine in Advanced Solid Tumors
Brief Summary: This phase I trial is studying the side effects and the best dose of veliparib when given together with capecitabine and oxaliplatin in treating patients with advanced solid tumors. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with capecitabine and oxaliplatin may kill more tumor cells.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To determine the dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of ABT-888 (veliparib) in combination with oxaliplatin and capecitabine in advanced solid tumors.
SECONDARY OBJECTIVES:
I. To evaluate the pharmacokinetics of ABT-888, oxaliplatin, and capecitabine when administered concomitantly.
II. To evaluate the safety and tolerability of the ABT-888 in combination with capecitabine and oxaliplatin.
III. To assess for evidence of anti-tumor activity with this combination, per tumor measurements using RECIST criteria, in these patients.
TERTIARY OBJECTIVES:
I. To assess the inhibition of poly(ADP-ribose) polymerase (PARP) in peripheral blood mononuclear cells secondary to treatment with ABT-888.
II. To determine the pharmacokinetics of ABT-888 in combination with oxaliplatin and capecitabine and the relation to treatment side effects.
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive veliparib orally (PO) twice daily and capecitabine PO twice daily on 1-7 and 15-21, and oxaliplatin intravenously (IV) over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and urine sample collection at baseline and periodically during study for pharmacokinetic and poly (ADP-ribose) polymerase (PARP) inhibition studies.
Original Primary Outcome:
- Maximum-tolerated dose of veliparib in combination with oxaliplatin and capecitabine
- Dose-limiting toxicities of veliparib in combination with oxaliplatin and capecitabine
Current Secondary Outcome:
- Pharmacokinetics of veliparib administered concomitantly with oxaliplatin and capecitabine [ Time Frame: At baseline, at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours of days 1 and 7 ]Graphical displays of individual, mean, and median plasma concentration over time will be presented at each ABT-888 dose level and overall in the entire group. Descriptive summaries for each pharmacokinetic endpoint will be presented by ABT-888 dose level.
- Safety and tolerability as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]Reported in tabular format, both per dose level, as well as in the aggregate cohort.
- Anti-tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 30 days ]Anti-tumor responses will be summarized using descriptive statistics and will be presented in tables. In addition, two-sided 90% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be obtained.
Original Secondary Outcome:
- Pharmacokinetics of veliparib administered concomitantly with oxaliplatin and capecitabine
- Safety and tolerability
- Anti-tumor response
Information By: National Cancer Institute (NCI)
Dates:
Date Received: November 2, 2010
Date Started: October 2010
Date Completion:
Last Updated: April 1, 2014
Last Verified: October 2013
