A Randomized Phase III Trial of Endocrine Therapy plus Entinostat/Placebo in Postmenopausal Patients with Hormone Receptor-Positive Advanced Breast Cancer

This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes or another place in the body. Estrogen can cause the growth of breast cancer cells. Endocrine therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether exemestane is more effective with or without entinostat in treating breast cancer.

Inclusion Criteria:

• Estrogen receptor (ER) and/or progesterone receptor (PR) positive histologically confirmed adenocarcinoma of the breast with staining of >= 1% cells will be considered positive; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
• Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
• Patients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is not possible; lesions must be evaluated =< 4 weeks prior to study randomization; diagnostic-quality computed tomography (CT) scans with both oral and intravenous (IV) contrast are the expected radiologic method, unless an alternative is approved
• Pre/peri- and postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:
◦ Age >= 55 years and one year or more of amenorrhea
◦ Age < 55 years and one year or more of amenorrhea, with estradiol < 20 pg/ml
◦ Age < 55 with prior hysterectomy but intact ovaries, with estradiol < 20 pg/ml
◦ Prior bilateral oophorectomy NOTE: Women who do not fit the criteria for being postmenopausal as above are deemed pre-or peri-menopausal; pre/perimenopausal women and all men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; pre/perimenopausal women must have commenced treatment with LHRH agonist at least 4 weeks prior to randomization; if patients have received alternative LHRH agonist prior to study entry, they must switch to goserelin for the duration of the trial
• Patients must not have known central nervous system metastasis or a history of central nervous system (CNS) metastases; patients with leptomeningeal disease are not eligible
• Patients must be disease-free of prior invasive malignancies for > 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
◦ NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer
• Patients must meet at least one of the following criteria:
◦ Disease progression any time after non-steroidal aromatase inhibitor (AI) use in the advanced disease setting
◦ Relapse while on or within =< 12 months of end of adjuvant non-steroidal AI therapy with no prior endocrine therapy for advanced disease
• Patients must have no known allergies to imidazole drugs (e.g. clotrimazole, ketoconazole, miconazole, econazole, sulconazole, ticonazole, or terconazole), exemestane or entinostat
Phase III
Alison Conlin, M.D.
ECOG (Eastern Cooperative Oncology Group)
Nikki Moxon

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.