Clinical trial NCT00676663: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Estrogen Receptor-Positive Breast Cancer
Breast Cancer, Estrogen Receptor-Positive
ER+ Breast Cancer
Keywords: Breast Neoplasms
Breast Tumor
Mammary Neoplasms
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-05-13
Enrollment: 130
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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)
measure: Clinical Benefit Rate (CBR)
timeFrame: From date of randomization to discontinuation due to disease progression or intolerable AE up to primary completion date (Median follow-up 6 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years)
Other outcomes:
measure: Overall Survival (OS)
timeFrame: 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)
Locations:
city: Greenbrae
country: United States
facility: California Cancer Care
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Tampa
country: United States
facility: University of Southern Florida -Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Indiana Cancer Pavilion
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Kansas City
country: United States
facility: Kansas City Cancer Center
state: Missouri
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern New Jersey
state: New Jersey
city: Charlotte
country: United States
facility: Carolinas Healthcare System Clinical Trials
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: McAllen
country: United States
facility: South Texas Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Kennewick
country: United States
facility: Columbia Basin Hematology & Oncology
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center
state: Washington
city: Oshawa
country: Canada
facility: RSM Durham Regional Cancer Center - Lakeridge Health
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre
state: Ontario
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Pardubice
country: Czechia
facility: Radiologicke centrum Multiscan, s.r.o.
city: Praque
country: Czechia
facility: Fakultani Nemocnice Kralavske Vinohadry
city: Budapest
country: Hungary
facility: Allami Egeszseguegi Koezpont
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Radiologicke centrum Multiscan
city: Szekszárd
country: Hungary
facility: Clinfan Ltd SMO, County Hospital Szekszard
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Blokhin Russian Oncology Research Center of Russian Academy of Medical Sciences
city: Saint Petersburg
country: Russian Federation
facility: Russian Research Centre of Radiology and Surgery
city: Saint-Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Stavropol
country: Russian Federation
facility: Stavropol Territory Clinical Oncology Dispensary
Study officials:
affiliation: Sarah Cannon Cancer Center
name: Denise Yardley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.