Cyclophosphamide With or Without Veliparib in Patients With Locally Advanced or Metastatic Breast Cancer
This randomized phase I/II trial studies cyclophosphamide with or without veliparib in treating patients with locally advanced or metastatic breast cancer. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cyclophosphamide is more effective with or without veliparib in treating breast cancer.
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
Male Breast Cancer
Progesterone Receptor-positive Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||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|
- Recommended phase II dose of veliparib that may be used with metronomic cyclophosphamide [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]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.
- Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: From first treatment day until objective or disease progression or death from any cause, assessed up to 6 months ] [ Designated as safety issue: No ]The PFS distributions of the two treatment arms will be estimated by the Kaplan-Meier method. Ninety-five percent confidence intervals for the Kaplan-Meier estimates will be calculated using Greenwood's approach. The log-rank test will be applied to compare the PFS distributions between the two treatment arms and the Cox Proportional hazards model will be fit to the data to estimate the hazard ratio.
- Clinical response (complete or partial response) according to RECIST version 1.1 [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]Clinical response and benefit rates in each group will be estimated by computing proportions and corresponding 95% confidence intervals. Rates will be compared between groups using the Fisher's exact test.
- Overall survival [ Time Frame: Time from treatment initiation to death, assessed up to 4 years ] [ Designated as safety issue: No ]Overall survival will be analyzed using standard survival analytic approaches including the Kaplan-Meier method and the log-rank test.
|Study Start Date:||May 2011|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm I (cyclophosphamide, veliparib)
Patients receive cyclophosphamide PO QD and veliparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other Name: ABT-888Drug: cyclophosphamide
Other Names:Other: laboratory biomarker analysis
Active Comparator: Arm II (cyclophosphamide, placebo)
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.
Other Names:Other: placebo
Other Name: PLCBOther: laboratory biomarker analysis
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 II)
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 cyclophosphamide.
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 unacceptable toxicity.
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.
|United States, Connecticut|
|University of Connecticut||Active, not recruiting|
|Farmington, Connecticut, United States, 06030|
|United States, New York|
|Albert Einstein College of Medicine||Recruiting|
|Bronx, New York, United States, 10461|
|Contact: Eleni Andreopoulou 718-904-2730 firstname.lastname@example.org|
|Principal Investigator: Eleni Andreopoulou|
|Montefiore Medical Center||Recruiting|
|Bronx, New York, United States, 10467-2490|
|Contact: Eleni Andreopoulou 718-904-2555 email@example.com|
|Principal Investigator: Eleni Andreopoulou|
|Maimonides Medical Center||Active, not recruiting|
|Brooklyn, New York, United States, 11219|
|New York University Langone Medical Center||Active, not recruiting|
|New York, New York, United States, 10016|
|Mount Sinai Medical Center||Active, not recruiting|
|New York, New York, United States, 10029|
|Columbia University Medical Center||Active, not recruiting|
|New York, New York, United States, 10032|
|Weill Medical College of Cornell University||Active, not recruiting|
|New York, New York, United States, 10065|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Active, not recruiting|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Eleni Andreopoulou||Montefiore Medical Center|