Cyclophosphamide and Veliparib in Treating Patients With Locally Advanced or Metastatic Breast Cancer
|ClinicalTrials.gov Identifier: NCT01351909|
Recruitment Status : Active, not recruiting
First Posted : May 11, 2011
Last Update Posted : May 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|HER2/Neu Negative Recurrent Breast Carcinoma Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7||Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Drug: Veliparib||Phase 1|
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.
I. To determine whether the macroH2A1.1 and poly (adenosine diphosphate [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 dose-escalation study.
Patients receive veliparib orally (PO) once daily (QD) and cyclophosphamide PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of Low-Dose Cyclophosphamide in Combination With Veliparib (ABT-888) in HER2/Neu-Negative Metastatic Breast Cancer|
|Actual Study Start Date :||May 2, 2011|
|Actual Primary Completion Date :||November 25, 2016|
Experimental: Treatment (veliparib, cyclophosphamide)
Patients receive veliparib orally PO QD and cyclophosphamide PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Recommended phase II dose of veliparib and cyclophosphamide [ Time Frame: 21 days ]The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for adverse events reporting.
- Clinical response (complete or partial response) according to RECIST version 1.1 [ Time Frame: Up to 24 weeks ]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 6 years ]Overall survival will be analyzed using standard survival analytic approaches including the Kaplan-Meier method and the log-rank test.
- MacroH2A1.1 expression levels [ Time Frame: Up to 6 years ]Expression levels of macroH2A1.1 will be compared between patients with and without clinical benefit using the two-sample T-test or Wilcoxon rank sum test, depending on the distribution of the data. Logistic regression models will also be fit to the data to adjust for potential confounders in the analysis.
- PARP1 expression status [ Time Frame: Up to 6 years ]Expression levels of PARP1 will be compared between patients with and without clinical benefit using the two-sample T-test or Wilcoxon rank sum test, depending on the distribution of the data. Logistic regression models will also be fit to the data to adjust for potential confounders in the analysis.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01351909
|United States, New York|
|Montefiore Medical Center-Einstein Campus|
|Bronx, New York, United States, 10461|
|Montefiore Medical Center-Weiler Hospital|
|Bronx, New York, United States, 10461|
|Montefiore Medical Center - Moses Campus|
|Bronx, New York, United States, 10467|
|Laura and Isaac Perlmutter Cancer Center at NYU Langone|
|New York, New York, United States, 10016|
|Columbia University/Herbert Irving Cancer Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Joseph Sparano||Montefiore Medical Center - Moses Campus|