Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing

Inclusion criteria

• Postmenopausal female patients.
• Histologically or cytologically confirmed estrogen receptor-positive (ER+) breast cancer.
• Progressive disease (PD) after at least 3 months on treatment with a 3rd generation AI in the advanced disease setting as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• At least 1 measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography (CT) scan with the last imaging performed within 4 weeks prior to study entry. If there is only one measurable lesion and it is located in previously irradiated field, it must have demonstrated progression according to RECIST criteria.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Laboratory parameters:

• Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x10^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without the use of hematopoietic growth factors.
• Creatinine less than 2.5 times the upper limit of normal for the institution.
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of normal for the institution.
• Able to understand and give written informed consent and comply with study procedures.

Exclusion criteria

• Discontinuation of AI therapy prior to study entry.
• Less than 3 months treatment with most recent AI.
• Rapidly progressive, life-threatening metastases, including any of the following:

• Symptomatic lymphangitic metastases.
• Patients with known active brain or leptomeningeal involvement.
• More than one prior chemotherapy for metastatic disease.
• Any chemotherapy within 3 months prior to study.
• Radiotherapy to measurable lesion within 2 months prior to study.
• Bisphosphonates initiated within 4 weeks prior to study start.
• Allergy to benzamides or inactive components of study drug.
• Previous treatment with entinostat or any other histone deacetylase (HDAC) inhibitor including valproic acid.
• Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid or other systemic cancer agents
• Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator:

• Myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval >0.47 second.
• Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection,
• Other active malignancy within 5 years excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ).
• Patient currently is enrolled in (or completed within 30 days before study drug administration) another investigational drug study.