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Trial record 1 of 1 for:    ENCORE 301
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Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer (ENCORE301)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00676663
Recruitment Status : Completed
First Posted : May 13, 2008
Results First Posted : October 24, 2019
Last Update Posted : October 24, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Estrogen Receptor-Positive Breast Cancer Breast Cancer, Estrogen Receptor-Positive ER+ Breast Cancer Drug: entinostat Drug: exemestane Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : June 13, 2008
Actual Primary Completion Date : January 29, 2011
Actual Study Completion Date : November 26, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Exemestane

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 Name: SNDX-275

Drug: exemestane
Exemestane 25 mg tablet orally once daily
Other Name: 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 Name: Aromasin®

Drug: Placebo
Placebo-matching entinostat tablet orally once per week




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Other Outcome Measures:
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00676663


Locations
Show Show 38 study locations
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
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Principal Investigator: Denise Yardley, MD Sarah Cannon Cancer Center
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00676663    
Other Study ID Numbers: SNDX-275-0301
2009-012623-28 ( EudraCT Number )
First Posted: May 13, 2008    Key Record Dates
Results First Posted: October 24, 2019
Last Update Posted: October 24, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Syndax Pharmaceuticals:
Breast Neoplasms
Breast Tumor
Mammary Neoplasms
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Entinostat
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Histone Deacetylase Inhibitors