Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer

Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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. Additionally, patients also undergo collection of blood sample, positron emission tomography (PET)/computed tomography (CT) throughout the study.

After completion of study treatment, patients are followed up for 12 weeks.