Sequential Phase I - Randomized Phase II, Double-Blind, Placebo-Controlled Trial of Cyclophosphamide Alone or in Combination With Veliparib (ABT-888) in ER and/or PR-Positive and HER2/Neu-Negative Metastatic Breast Cancer
I. To determine the recommended phase II dose of veliparib (ABT-888) that can be combined
with metronomic dose cyclophosphamide in patients with metastatic breast cancer. (Phase I)
II. To determine if the addition of veliparib (ABT-888) to metronomic dose cyclophosphamide
improves median progression free survival (PFS) compared with cyclophosphamide alone in
patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive, human
epidermal growth factor receptor 2 (Her2)-negative metastatic breast cancer who progressed
on at least two lines of prior chemotherapy and one line of prior endocrine therapy. (Phase
I. To determine if the addition veliparib (ABT-888) to cyclophosphamide chemotherapy
improves the response rate.
II. To determine if the addition veliparib (ABT-888) to cyclophosphamide chemotherapy
improves the clinical benefit rate (defined as objective response plus stable disease for at
least 24 weeks from day +1) III. To determine the survival in patients treated with
cyclophosphamide alone and cyclophosphamide plus veliparib (ABT-888).
IV. To determine the adverse event profile in patients treated with cyclophosphamide alone
and cyclophosphamide plus veliparib (ABT-888).
I. To determine whether the macroH2A1.1 and poly (ADP-ribose) polymerase 1 (PARP1)
expression status in archival paraffin embedded tumor specimens from either the primary
tumor or metastatic disease is predictive of clinical benefit with veliparib (ABT-888) plus
OUTLINE: This is a multicenter study. Patients are stratified according to measurable
disease (yes vs no) and ECOG performance status (0 vs 1 or 2). Patients are randomized to 1
of 2 treatment arms.
ARM I: Patients receive cyclophosphamide orally (PO) once daily (QD) and veliparib PO QD on
days 1-21. Courses repeat every 21 days in the absence of disease progression or
ARM II: Patients receive placebo PO QD on days 1-21 and cyclophosphamide as in arm I.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients may undergo peripheral blood mononuclear cells sample collection for correlative
studies. Archived tissue from primary tumor or a biopsy sample from metastatic disease may
also be collected.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Recommended phase II dose of veliparib that may be used with metronomic cyclophosphamide
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
Montefiore Medical Center
United States: Food and Drug Administration
|Weill Medical College of Cornell University||New York, New York 10021|
|Maimonides Medical Center||Brooklyn, New York 11219|
|Mount Sinai Medical Center||New York, New York 10029|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|University of Connecticut||Farmington, Connecticut 06032|
|New York University Langone Medical Center||New York, New York 10016|
|Columbia University Medical Center||New York, New York 10032|