Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors
|Adenocarcinoma of the Pancreas Adenocarcinoma of the Stomach BRCA1 Mutation Carrier BRCA2 Mutation Carrier Ovarian Mucinous Cystadenocarcinoma Recurrent Breast Cancer Recurrent Colon Cancer Recurrent Gastric Cancer Recurrent Ovarian Epithelial Cancer Recurrent Ovarian Germ Cell Tumor Recurrent Pancreatic Cancer Recurrent Rectal Cancer Stage IA Breast Cancer Stage IB Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Stage IV Colon Cancer Stage IV Gastric Cancer Stage IV Ovarian Epithelial Cancer Stage IV Ovarian Germ Cell Tumor Stage IV Pancreatic Cancer Stage IV Rectal Cancer Unspecified Adult Solid Tumor, Protocol Specific||Drug: veliparib Drug: capecitabine Drug: oxaliplatin Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of ABT-888 in Combination With Oxaliplatin and Capecitabine in Advanced Solid Tumors|
- Maximum-tolerated (MTD) dose of veliparib in combination with oxaliplatin and capecitabine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]MTD defined as the dose level at which less than one-third of patients experience a dose-limiting toxicity (DLT).
- Dose-limiting toxicities of veliparib in combination with oxaliplatin and capecitabine as assessed by NCI CTCAE version 4.0 [ Time Frame: 28 days ]
- 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.
|Study Start Date:||October 2010|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib, capecitabine, oxaliplatin)
Patients receive veliparib PO twice daily and capecitabine PO twice daily on 1-7 and 15-21, and oxaliplatin IV over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: ABT-888Drug: capecitabine
Other Names:Drug: oxaliplatin
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
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.
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.
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.
After completion of study therapy, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01233505
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||William Schelman||University of Wisconsin, Madison|