Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer (ENCORE301)

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; ER+ Breast Cancer; Estrogen Receptor-Positive Breast Cancer; Breast Cancer, Estrogen Receptor-Positive
• Intervention / Treatment: Drug: entinostat; Drug: exemestane; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exemestane 25 mg + Entinostat 5 mg; 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; Entinostat 5 mg tablet orally once per week; Other Names: SNDX-275; Drug: exemestane; Exemestane 25 mg tablet orally once daily; Other Names: Aromasin®
Placebo Comparator: Exemestane 25 mg + 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.	Drug: exemestane; Exemestane 25 mg tablet orally once daily; Other Names: Aromasin®; Drug: Placebo; Placebo-matching entinostat tablet orally once per week

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the number of months elapsed between the date of randomization and the date of death (whatever the cause).	First dose of study drug to end of study (Median follow-up 24 months in the EE arm and 26.4 months in the EP arm)

Collaborators and Investigators

• Sponsor: Syndax Pharmaceuticals
• Investigators: Principal Investigator: Denise Yardley, MD, Sarah Cannon Cancer Center

Publications and helpful links

General Publications

• Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM, Cruickshank S, Miller KD, Lee MJ, Trepel JB. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol. 2013 Jun 10;31(17):2128-35. doi: 10.1200/JCO.2012.43.7251. Epub 2013 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2008
• Primary Completion (Actual): January 29, 2011
• Study Completion (Actual): November 26, 2012

Study Registration Dates

• First Submitted: May 9, 2008
• First Submitted That Met QC Criteria: May 9, 2008
• First Posted (Estimate): May 13, 2008

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Breast Neoplasms; Breast Tumor; Mammary Neoplasms
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Histone Deacetylase Inhibitors; Exemestane; Entinostat
• Other Study ID Numbers: SNDX-275-0301; 2009-012623-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No