Phase II Study of Azacitidine and Entinostat (SNDX-275) in Patients With Advanced Breast Cancer
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
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Confirmed response rate (complete or partial response noted as the objective status on two consecutive evaluations at least 4 weeks apart) assessed by RECIST
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.
Up to 3 years
Johns Hopkins University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|City of Hope||Duarte, California 91010|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|Metro-Minnesota CCOP||St. Louis Park, Minnesota|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Unity Hospital||Fridley, Minnesota 55432|
|Magee-Womens Hospital of UPMC||Pittsburgh, Pennsylvania 15213|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion||Aurora, Colorado 80045|
|Siteman Cancer Center at Washington University||Saint Louis, Missouri 63110|