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

Breast Cancer Clinical Trial

— ENCORE301  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676663
• Other study ID #: SNDX-275-0301
• Secondary ID: 2009-012623-28
• Status: Completed
• Phase: Phase 2
• Start date: June 13, 2008
• Est. completion date: November 26, 2012

Study information

• Verified date: April 2022
• Source: Syndax Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: November 26, 2012
• Est. primary completion date: January 29, 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• entinostat
Entinostat 5 mg tablet orally once per week
• exemestane
Exemestane 25 mg tablet orally once daily
• Placebo
Placebo-matching entinostat tablet orally once per week

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hungary,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)