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

Phase 2

Completed

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

Interventions: Drug: entinostat
Drug: Placebo
Drug: exemestane

Registration Number: NCT00676663

Lead Sponsor: Syndax Pharmaceuticals

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 130

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exemestane 25 mg + Placebo	Placebo	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.
Exemestane 25 mg + Entinostat 5 mg	exemestane	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.
Exemestane 25 mg + Entinostat 5 mg	entinostat	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.
Exemestane 25 mg + Placebo	exemestane	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	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)	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years)	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.
Clinical Benefit Rate (CBR)	From date of randomization to discontinuation due to disease progression or intolerable AE up to primary completion date (Median follow-up 6 months)	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.

Trial Locations

Locations (38): Chattanooga Oncology Hematology Associates
🇺🇸
Chattanooga, Tennessee, United States
Florida Cancer Specialists
🇺🇸
Fort Myers, Florida, United States
Memorial Cancer Institute
🇺🇸
Hollywood, Florida, United States
RSM Durham Regional Cancer Center - Lakeridge Health
🇨🇦
Oshawa, Ontario, Canada
Hematology-Oncology Associates of Northern New Jersey
🇺🇸
Morristown, New Jersey, United States
Fakultni nemocnice Olomouc
🇨🇿
Olomouc, Czechia
Indiana University Indiana Cancer Pavilion
🇺🇸
Indianapolis, Indiana, United States
Oncology Hematology Care
🇺🇸
Cincinnati, Ohio, United States
Sarah Cannon Cancer Center
🇺🇸
Nashville, Tennessee, United States
Puget Sound Cancer Center
🇺🇸
Seattle, Washington, United States
St. Joseph's Health Centre
🇨🇦
Toronto, Ontario, Canada
California Cancer Care
🇺🇸
Greenbrae, California, United States
Scripps Health
🇺🇸
La Jolla, California, United States
Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
Palm Beach Cancer Institute
🇺🇸
West Palm Beach, Florida, United States
Medical College of Georgia
🇺🇸
Augusta, Georgia, United States
University of Maryland Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Carolinas Healthcare System Clinical Trials
🇺🇸
Charlotte, North Carolina, United States
Cancer Centers of the Carolinas
🇺🇸
Greenville, South Carolina, United States
Virginia Cancer Institute
🇺🇸
Richmond, Virginia, United States
South Texas Cancer Center
🇺🇸
McAllen, Texas, United States
Columbia Basin Hematology & Oncology
🇺🇸
Kennewick, Washington, United States
Radiologicke centrum Multiscan, s.r.o.
🇨🇿
Pardubice, Czechia
Allami Egeszseguegi Koezpont
🇭🇺
Budapest, Hungary
Fakultani Nemocnice Kralavske Vinohadry
🇨🇿
Praque, Czechia
Semmelweis Egyetem
🇭🇺
Budapest, Hungary
Radiologicke centrum Multiscan
🇭🇺
Debrecen, Hungary
Clinfan Ltd SMO, County Hospital Szekszard
🇭🇺
Szekszárd, Hungary
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺
Arkhangelsk, Russian Federation
Blokhin Russian Oncology Research Center of Russian Academy of Medical Sciences
🇷🇺
Moscow, Russian Federation
Russian Research Centre of Radiology and Surgery
🇷🇺
Saint Petersburg, Russian Federation
Leningrad Regional Oncology Dispensary
🇷🇺
Saint-Petersburg, Russian Federation
Stavropol Territory Clinical Oncology Dispensary
🇷🇺
Stavropol, Russian Federation
Kansas City Cancer Center
🇺🇸
Kansas City, Missouri, United States
University of Southern Florida -Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Wake Forest University Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
University of Colorado
🇺🇸
Aurora, Colorado, United States
Rocky Mountain Cancer Center
🇺🇸
Denver, Colorado, United States