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

• ClinicalTrials.gov Identifier: NCT00676663
• Recruitment Status: Completed
• First Posted: May 13, 2008
• Results First Posted: October 24, 2019
• Last Update Posted: May 11, 2022
• Sponsor: Syndax Pharmaceuticals
• Information provided by (Responsible Party): Syndax Pharmaceuticals

Tracking Information

• First Submitted Date: May 9, 2008
• First Posted Date: May 13, 2008
• Results First Submitted Date: October 24, 2018
• Results First Posted Date: October 24, 2019
• Last Update Posted Date: May 11, 2022
• Actual Study Start Date: June 13, 2008
• Actual Primary Completion Date: January 29, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2019)

Progression-free Survival (PFS) [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: May 9, 2008): To compare the efficacy of exemestane alone with exemestane plus SNDX-275, as determined by the duration of progression free survival (PFS) measured from the date of randomization.

Current Secondary Outcome Measures (submitted: October 3, 2019)

• Objective Response Rate (ORR) [ Time Frame: 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.
• Clinical Benefit Rate (CBR) [ Time Frame: 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.
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: October 3, 2019)

Overall Survival (OS) [ Time Frame: 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) ]

OS was defined as the number of months elapsed between the date of randomization and the date of death (whatever the cause).

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: entinostat
  Entinostat 5 mg tablet orally once per week
  Other Name: SNDX-275
• Drug: exemestane
  Exemestane 25 mg tablet orally once daily
  Other Name: Aromasin®
• Drug: Placebo
  Placebo-matching entinostat tablet orally once per week

Study Arms

• 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.
  Interventions:

  • Drug: entinostat
  • Drug: exemestane
• 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.
  Interventions:

  • Drug: exemestane
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 19, 2014): 130
• Original Estimated Enrollment (submitted: May 9, 2008): 114
• Actual Study Completion Date: November 26, 2012
• Actual Primary Completion Date: January 29, 2011 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Hungary, Russian Federation, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00676663
• Other Study ID Numbers: SNDX-275-0301; 2009-012623-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Syndax Pharmaceuticals
• Original Responsible Party: Judy Billingsley, Clinical Program Manager, Syndax Pharmaceuticals, Inc.
• Current Study Sponsor: Syndax Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Denise Yardley, MD; Sarah Cannon Cancer Center

• PRS Account: Syndax Pharmaceuticals
• Verification Date: April 2022