Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer
This phase II trial studies how well giving azacitidine and entinostat work in treating patients with advanced breast cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.
Estrogen Receptor-negative Breast Cancer
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
Male Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Triple-negative Breast Cancer
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Azacitidine and Entinostat (SNDX-275) in Patients With Advanced Breast Cancer|
- Confirmed response rate (complete or partial response noted as the objective status on two consecutive evaluations at least 4 weeks apart) assessed by RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]The proportion of successes will be estimated independently for each cohort by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
- Progression-free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated using the method of Kaplan-Meier.
- Clinical benefit rate estimated by the number of patients who achieve a confirmed response plus the number of patients who have stable disease for a duration of at least 6 months divided by the total number of evaluable patients [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculated.
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (entinostat and azacitidine)
Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring. Patients undergo blood and tumor tissue sample collection at baseline and periodically during therapy for correlative studies.
Other Names:Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: azacitidine
I. To evaluate objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST) criteria of the combination of Azacitidine (5-AZA) and entinostat in women with advanced breast cancer; triple-negative and hormone-refractory.
I. To determine the safety and tolerability of the combination of 5-AZA and entinostat in women with advanced breast cancer.
II. To determine progression-free survival, overall survival, and clinical benefit rate of the combination of 5-AZA and entinostat.
I. To collect safety and toxicity data as well as the feasibility and response rate where hormonal therapy is added to the combination under investigation at the time of progressive disease. (Exploratory) II. To determine the pharmacokinetic profile of 5-AZA (full profile) and entinostat (trough concentrations) in patients with advanced breast cancer. (Exploratory) III. To assess serum cytidine deaminase pharmacogenetics and phenotypic activity as a potential biomarker of response to 5-AZA. (Exploratory) IV. To evaluate baseline and change in candidate gene re-expression (e.g., ERalpha, RARbeta) in malignant tissue obtained from selected patients through fine-needle aspiration (FNA) and core biopsy, prior to and following combination therapy. (Exploratory) V. To evaluate baseline and change in gene methylation silencing in circulating deoxyribonucleic acid (DNA) obtained prior to and following combination therapy. (Exploratory) VI. To evaluate baseline and change in gene methylation in malignant tissue obtained through FNA and core biopsy. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (triple negative vs resistant).
Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10, and entinostat orally (PO) on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring. Patients undergo blood and tumor tissue sample collection at baseline and periodically during therapy for correlative studies.
After completion of study therapy, patients are followed up every 3-6 months for up to 3 years.
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|University of Southern California|
|Los Angeles, California, United States, 90033|
|UC Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287|
|United States, Minnesota|
|Fridley, Minnesota, United States, 55432|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, Pennsylvania|
|Magee-Womens Hospital of UPMC|
|Pittsburgh, Pennsylvania, United States, 15213|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Vered Stearns||Johns Hopkins University|