Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter Study of Exemestane With and Without SNDX-275 in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer, Progressing on Treatment With a Non-Steroidal Aromatase Inhibitor

Conditions
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Breast Cancer, Estrogen Receptor-Positive Breast Cancer, Breast Cancer, Estrogen Receptor-Positive, ER+ Breast Cancer

Intervention / Treatment
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* Drug: entinostat
* Drug: exemestane
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exemestane 25 mg + Entinostat 5 mg<br>Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first. | Drug: entinostat<br>* Entinostat 5 mg tablet orally once per week<br>* Other names: SNDX-275;Drug: exemestane<br>* Exemestane 25 mg tablet orally once daily<br>* Other names: Aromasin®;|
| Placebo Comparator: Exemestane 25 mg + Placebo<br>Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first. | Drug: exemestane<br>* Exemestane 25 mg tablet orally once daily<br>* Other names: Aromasin®;Drug: Placebo<br>* Placebo-matching entinostat tablet orally once per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause. | From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with response during treatment classified as complete response (CR) or partial response (PR), as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | From date of randomization to discontinuation due to disease progression or intolerable Adverse Event (AE) up to primary completion date (Median follow-up 6 months) | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with overall response (CR + PR) plus stable disease (SD) for 6 months as assessed by the investigator based on RECIST, version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | From date of randomization to discontinuation due to disease progression or intolerable AE up to primary completion date (Median follow-up 6 months) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. Abnormal clinical laboratory findings determined by the investigator to be clinically significant were recorded as AEs. A TEAE is an AE that starts after the administration of study drug. A SAE is any AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth effect or other significant medical hazard. | First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Neoplasms, Breast Tumor, Mammary Neoplasms