Veliparib and Carboplatin in Treating Women With HER2-Negative Metastatic Breast Cancer
This phase I clinical trial is studying the side effects and best dose of veliparib when given with carboplatin and to see how well they work in treating women with human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Veliparib may help carboplatin work better by making tumor cells more sensitive to the drug.
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Estrogen Receptor-negative Breast Cancer
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Other: fluorine F 18 fluorothymidine
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:||A Phase 1 Dose-escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer|
- Number and severity of toxicity incidents to measure the safety and tolerability of this treatment combination for the treatment of HER2 negative metastatic breast cancer [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
- Clinical response (complete and partial response as well as stable and progressive disease) [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
|Study Start Date:||November 2010|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib, F 18 fluorothymidine, carboplatin)
Patients receive carboplatin IV over 1 hour on day 1 and veliparib PO twice daily on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.
Other Name: ABT-888Other: fluorine F 18 fluorothymidine
Undergo fluorothymidine PET scan
Other Names:Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: carboplatin
I. To determine the recommended phase II dose of veliparib along with carboplatin on a 14-day and 21-day schedule in patients with Her2 negative metastatic breast cancer that are estrogen receptor (ER)/progesterone receptor(PR) negative or ER and/or PR positive with defects in Fanconi Anemia (FA) pathway repair genes.
II. To determine the safety and tolerability of combining veliparib on a 14-day and 21-day schedule with carboplatin in this patient population.
III. To determine the preliminary efficacy of this combination in this patient population.
I. To determine the pharmacodynamic endpoints of poly(ADP-ribose) polymerase (PARP) inhibition in the tumor by using, A) 3'-[F-18]Fluoro-3'-deoxythymidine Positron Emission Tomography (FLT-PET) of the target lesions, B) circulating tumor cells to detect the induction of the histone variant gammaH2AX, and C) peripheral blood mononuclear cells to assess poly ADP-Ribose (PAR) levels.
II. To determine biomarkers in the primary tumor that may predict antitumor responses to PARP inhibition such as BRCA1/2 protein, FANCD2 nuclear foci formation and expression of miR 155.
OUTLINE: This is a multicenter, dose-escalation study of veliparib.
Patients receive carboplatin intravenously (IV) over 1 hour on day 1 and veliparib orally (PO) twice daily on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.
After completion of study treatment, patients are followed up for 12 weeks.
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center at Georgetown University||Recruiting|
|Washington, District of Columbia, United States, 20057|
|Contact: Claudine Isaacs 202-444-3677 firstname.lastname@example.org|
|Principal Investigator: Claudine Isaacs|
|United States, New York|
|Montefiore Medical Center||Recruiting|
|Bronx, New York, United States, 10467-2490|
|Contact: Eleni Andreopoulou 718-904-2555 email@example.com|
|Principal Investigator: Eleni Andreopoulou|
|United States, Ohio|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Bhuvaneswari Ramaswamy 614-293-6401 Bhuvaneswari.Ramaswamy@osumc.edu|
|Principal Investigator: Bhuvaneswari Ramaswamy|
|Principal Investigator:||Bhuvaneswari Ramaswamy||Ohio State University|