Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer
This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin and to see how well they work in treating patients with human epidermal growth factor 2 (HER2)-negative breast cancer that has spread to other parts of the body. Carboplatin kills cancer cells by damaging the deoxyribonucleic acid (DNA) that lets the cancer cell survive and reproduce. The body has proteins that try to repair the damaged DNA. Veliparib may prevent these proteins from repairing the DNA so that carboplatin may be able to kill more tumor cells. Giving veliparib with carboplatin may kill more tumor cells than carboplatin alone.
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
Procedure: positron emission tomography
Other: 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|
- Incidence of adverse events to measure the safety and tolerability of this treatment combination [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]Number and severity of toxicity incidents will be tabulated. 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 guideline (version 1.1).
- PARP-1 activity [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Analysis will be descriptive and exploratory in nature. Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
- Thymidine kinase uptake on FLT-PET scans [ Time Frame: Up to 18 weeks (after course 3) ] [ Designated as safety issue: No ]Analysis will be descriptive and exploratory in nature. Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
- Circulating tumor cell markers [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Analysis will be descriptive and exploratory in nature. Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
|Study Start Date:||November 2010|
|Estimated Primary Completion Date:||January 2015 (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-888Drug: carboplatin
Other Names:Other: fluorine F 18 fluorothymidine
Other Names:Procedure: positron emission tomography
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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 gamma H2AX, 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 breast cancer 1/2, early onset (BRCA)1/2 protein, Fanconi anemia, complementation group D2 (FANCD2) nuclear foci formation and expression of micro-ribonucleic acid (RNA) 155 (miR 155).
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive carboplatin intravenously (IV) over 1 hour on day 1 and veliparib orally (PO) twice daily (BID) on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01251874
|United States, New York|
|Montefiore Medical Center - Moses Campus||Recruiting|
|Bronx, New York, United States, 10467-2490|
|Contact: Joseph A. Sparano 718-904-2555 email@example.com|
|Principal Investigator: Joseph A. Sparano|
|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|