A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer
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 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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Non-hematologic toxicities will be evaluated via the ordinal 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.
Up to 12 weeks post-treatment
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|
|Lombardi Comprehensive Cancer Center at Georgetown University||Washington, District of Columbia 20057|