Last updated on January 2019

Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic

Brief description of study

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.

Detailed Study Description


I. To evaluate whether the addition of entinostat to endocrine therapy (exemestane) improves progression-free survival (PFS) and/or overall survival (OS) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have previously progressed on a non-steroidal aromatase inhibitor (Al).


I. To evaluate the safety and tolerability of entinostat in combination with exemestane, and to compare the safety profile to that of endocrine therapy with placebo.

II. To evaluate the objective response rate of exemestane in combination with entinostat or placebo.

III. To evaluate whether the efficacy of exemestane with entinostat varies with changes in acetylation status in peripheral blood mononuclear cells (PBMCs).

IV. To evaluate the time to treatment deterioration (as defined by decrease in health-related quality of life [HRQL], progression, death) of exemestane + entinostat versus exemestane + placebo arms.

V. To evaluate the differences in overall health-related quality of life (HRQL) between the exemestane + entinostat versus exemestane + placebo arms.

VI. To evaluate the difference with respect to specific symptoms that are associated with entinostat, i.e., fatigue, nausea, anorexia and diarrhea, between the exemestane + entinostat versus exemestane + placebo arms.

VII. To measure adherence to protocol therapy. VIII. To evaluate the pharmacokinetics of entinostat in patients with advanced breast cancer.

IX. To evaluate what, if any, patient variables alter the pharmacokinetic profile of entinostat in patients with advanced breast cancer.


I. To collect archival tumor samples and germline deoxyribonucleic acid (DNA) to explore other potential biomarkers of therapeutic efficacy.

II. To collect patient ratings of adverse events (AEs) using select patient-reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items to evaluate the psychometric properties of PRO-CTCAE items and explore the incorporation of PRO-CTCAE items into a phase III double-blind placebo-controlled trial.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive exemestane orally (PO) once daily (QD) on days 1-28 and entinostat PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive exemestane as in Arm A and placebo PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

In both arms, pre/perimenopausal female patients and all male patients also receive goserelin acetate subcutaneously (SC) on day 1.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Clinical Study Identifier: NCT02115282

Contact Investigators or Research Sites near you

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Kathleen C. Toomey

Robert Wood Johnson University Hospital Somerset
Somerville, NJ United States

Recruitment Status: Closed

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