A Pilot and Phase II Study of Entinostat and Anastrozole/Tamoxifen in Women With Triple Negative Breast Cancer to Evaluate Biomarkers and Surrogates for Response
I. To evaluate the safety and tolerability of entinostat in combination with anastrozole or
tamoxifen. (Pilot) II. To determine the optimal dose of entinostat in combination with
anastrozole or tamoxifen for phase II. (Pilot) III. To determine baseline and percentage
change in proliferative index (Ki67) before and after treatment with entinostat and
anastrozole/tamoxifen in triple negative breast cancer (TNBC). (Phase II) IV. To determine
the estrogen receptor (ER) expression after treatment with entinostat and
anastrozole/tamoxifen in TNBC. (Phase II)
I. To evaluate baseline and change in the expression levels of progesterone receptor (PR),
human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR),
cytokeratin 5/6 (CK5/6), and aromatase before and after treatment with entinostat and
II. To assess baseline and change in tumor tissue histone H3 and H4 acetylation before and
after treatment with entinostat and anastrozole/tamoxifen.
III. To assess the clinical and pathological response to preoperative combination of
entinostat and anastrozole/tamoxifen in TNBC.
I. To correlate the levels of histone H3 and H4 acetylation in tumors with the changes in
Ki67 and ER.
II. To evaluate baseline and change in gene methylation silencing and expression of
candidate genes in tissues and in circulating DNA, including estrogen receptor (ER)-alpha,
ER-beta, RAR-beta, cyclin D2, Twist, RASSF1A, and HIN-1.
III. To correlate entinostat trough concentrations with histone H3 and H4 acetylation in
tumors as well as the change in Ki67 and ER.
IV. To evaluate baseline and change in the global gene expression profile before and after
treatment with entinostat and anastrozole/tamoxifen.
OUTLINE: This is a multicenter, pilot study followed by a phase II study.
Patients receive entinostat orally (PO) once daily on days 1, 8, 15, 22, and 29 and
anastrozole PO once daily on days 4-29. Patients then undergo mastectomy or lumpectomy.
Tumor tissue samples are collected at baseline or from original diagnosis, and during
surgery for correlative studies by IHC and RT-PCR. Blood samples are also collected at
baseline, on days 1 and 15, and during surgery for correlative studies.
After completion of study therapy, patients are followed up for 30 days.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of entinostat in combination with anastrozole (pilot)
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Michigan||Ann Arbor, Michigan 48109-0624|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|Northwestern Memorial Hospital||Chicago, Illinois 60611|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Central Illinois Hematology Oncology Center||Springfield, Illinois 62701|
|City of Hope||Duarte, California 91010|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|Illinois CancerCare-Peoria||Peoria, Illinois 61615|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|City of Hope Medical Group Inc||Pasadena, California 91105|
|Magee-Womens Hospital - University of Pittsburgh Medical Center||Pittsburgh, Pennsylvania 15213|
|University of Maryland Baltimore||Baltimore, Maryland 21201|
|University of California Davis Phase 2 Consortium||Sacramento, California 95817|