Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer
Condition: Breast Cancer; Estrogen Receptor-Positive Breast Cancer; Breast Cancer, Estrogen Receptor-Positive; ER+ Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: entinostat; exemestane; Placebo
Intervention description: Entinostat 5 mg tablet orally once per week; Exemestane 25 mg tablet orally once daily; Placebo-matching entinostat tablet orally once per week
Intervention MeSH terms: Exemestane; Entinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 130.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Neoplasms; Breast Tumor; Mammary Neoplasms

Summary:

      The purpose of this study is to evaluate the safety and efficacy of entinostat in combination
      with exemestane in the treatment of advanced breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal female patients

          -  Histologically or cytologically confirmed estrogen receptor positive (ER+) breast
             cancer

          -  Relapsed or progressed on prior treatment with aromatase inhibitor (AI)

          -  Metastatic disease must be measurable

          -  Patients receiving palliative radiation at the non-target lesions must have a 2 week
             wash out period following completion of the treatment prior to enrollment

          -  Patient may have had one prior chemotherapy as part of first line therapy as long as
             it was received before initiation of prior AI

          -  Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1

          -  Laboratory parameters: a)Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100.0 x 10^9/L; Absolute
             Neutrophil Count (ANC ≥) 1.5 x 10^9/L without the use of hematopoietic growth factors
             b)Creatinine less than 2.5 times the upper limit of normal for the institution
             c)Aspartate transaminase (AST) and alanine transaminase (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:

          -  Relapse on treatment with non-steroidal AI after less than 12 months for patients in
             the adjuvant setting

          -  Progressive disease after less than 3 months treatment with most recent AI for
             patients with metastatic disease

          -  Rapidly progressive, life-threatening metastases

          -  Any palliative radiotherapy to the measurable lesion

          -  Previous treatment with SNDX-275 or any other histone deacetylase (HDAC) inhibitor
             including valproic acid

          -  Allergy to benzamides or inactive components of the study drug

          -  A history of allergies to any active or inactive ingredients of exemestane

          -  Any concomitant medical condition that precludes adequate study treatment compliance

          -  Patient is currently enrolled in (or completed within 30 days before study drug
             administration) another investigational drug study

          -  Patient is currently receiving treatment with valproic acid, Zolinza (vorinostat) or
             any other HDAC inhibitor or deoxyribonucleic acid (DNA) methyltransferase inhibitor or
             any systemic anticancer treatment (with the exception of Lupron)