Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Hereditary Breast/Ovarian Cancer - BRCA1
Hereditary Breast/Ovarian Cancer - BRCA2
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Drug: vinorelbine tartrate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of ABT-888 in Combination With Cisplatin and Vinorelbine for Patients With Advanced Triple Negative Breast Cancer and/or BRCA-Mutation Associated Breast Cancer|
- MTD of veliparib, defined as the highest dose tested in which fewer than 33% of patients experienced dose-limiting toxicity attributable to the study regimen, when at least 6 patients were treated at that dose and were evaluable for toxicity [ Time Frame: Day 21 ]
- Toxicity profile, defined by the incidence of toxicity, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days post-treatment ]
- Pharmacokinetic (PK) parameters of veliparib in plasma and urine samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ]The PK parameters determined will be: AUC0-t (the area under the concentration-time curve over a dosing interval), Cmax (maximal concentration), Tmax (time to maximal concentration), Vd (volume of distribution), CL/F (oral clearance for veliparib), CL (clearance for cisplatin), and t1/2 (elimination half-life). To improve understanding of systemic bioavailability, the amount of veliparib excreted in the urine for each collection interval will be calculated by the product of urinary drug concentration and urine volume.
- Pharmacokinetic (PK) parameters of cisplatin in plasma samples [ Time Frame: Baseline and day 1 of courses 1 and 4 ]The PK parameters determined will be: AUC0-t, Cmax, Tmax, Vd, CL/F, CL, and t1/2 .
- Pharmacodynamic parameters of PARP inhibition [ Time Frame: Baseline and day 1 of courses 1 and 4 ]Assessed by measuring changes in PAR levels in peripheral blood mononuclear cells and in tumor tissue (if available).
- Progression-free survival [ Time Frame: The number of days from the date the subject started study drug to the date the subject experiences an event of disease progression, or to the date of death if disease progression is not reached, assessed up to 30 days ]Estimated using Kaplan-Meier methodology and 95% confidence interval.
- Time to disease progression [ Time Frame: The number of days from the date the subject started study drug to the date of the subject's disease progression, assessed up to 30 days ]Estimated using Kaplan-Meier methodology and 95% confidence interval.
- Proportion of patients achieving a complete response (CR) or partial response (PR) (objective response rate) [ Time Frame: Up to 30 days ]Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 and estimated with 95% confidence interval.
- Duration of overall response [ Time Frame: The number of days from the day the criteria are met for CR or PR (whichever is recorded first) to the date that progressive disease is objectively documented, assessed up to 30 days ]Estimated using Kaplan-Meier Methodology.
- ECOG performance status [ Time Frame: Up to 30 days ]Descriptive statistics will be summarized for each assessment.
|Study Start Date:||July 2010|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib with cisplatin and vinorelbine tartrate)
Patients receive veliparib PO BID on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin IV over 1 hour on day 1 and vinorelbine ditartrate IV over 10-20 minutes on days 1 and 8. Treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Treatment with veliparib alone may continue in the absence of disease progression or unacceptable toxicity.
Other Name: ABT-888Drug: cisplatin
Other Names:Drug: vinorelbine tartrate
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
I. To determine the maximum tolerated dose (MTD) of ABT-888 (veliparib) when administered daily for 14 days out of a 21 day cycle in combination with cisplatin and vinorelbine (vinorelbine ditartrate) in subjects with metastatic triple negative breast cancer (TNBC) and breast cancer (BRCA) mutation associated breast cancer.
I. Assess the pharmacokinetic profile of ABT-888 when combined with cisplatin and vinorelbine and the safety/tolerability profile of the combination.
II. Evaluate the level of poly ADP ribose polymerase (PARP) inhibition at each dose level to determine whether maximal PARP inhibition is achieved.
III. Identify the subgroup of triple negative breast cancer patients who will potentially derive the most benefits from PARP inhibition combined with platinum-based chemotherapy.
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive veliparib orally (PO) twice daily (BID) on days 1-14 (days 0-13 of course 1 only). Patients also receive cisplatin intravenously (IV) over 1 hour on day 1 and vinorelbine ditartrate IV over 10-20 minutes on days 1 and 8. Treatment repeats every 21 days for 6-10 courses in the absence of disease progression or unacceptable toxicity. Treatment with veliparib alone may continue in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01104259
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Jennifer Specht||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|