Breast CancerPhase 2ENCORE301NCT00676663
Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer
A Phase 2 study testing entinostat and exemestane in people with Breast Cancer and Estrogen Receptor-Positive Breast Cancer, run by Syndax Pharmaceuticals at 38 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Estrogen Receptor-Positive Breast Cancer, Breast Cancer, Estrogen Receptor-Positive
- What is being tested?
- entinostat and exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 38 sitesin 5 countries
- Study dates
- 13 Jun 2008to 26 Nov 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
38 sites in 5 countries.
38 sites in 5 countries
United States24 sites
Medical College of Georgia
Augusta, Georgia
University of Colorado
Aurora, Colorado
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland
Carolinas Healthcare System Clinical Trials
Charlotte, North Carolina
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee
Oncology Hematology Care
Cincinnati, Ohio
Rocky Mountain Cancer Center
Denver, Colorado
Florida Cancer Specialists
Fort Myers, Florida
California Cancer Care
Greenbrae, California
Cancer Centers of the Carolinas
Greenville, South Carolina
Memorial Cancer Institute
Hollywood, Florida
Indiana University Indiana Cancer Pavilion
Indianapolis, Indiana
Kansas City Cancer Center
Kansas City, Missouri
Columbia Basin Hematology & Oncology
Kennewick, Washington
Moores UCSD Cancer Center
La Jolla, California
Scripps Health
La Jolla, California
South Texas Cancer Center
McAllen, Texas
Hematology-Oncology Associates of Northern New Jersey
Morristown, New Jersey
Sarah Cannon Cancer Center
Nashville, Tennessee
Virginia Cancer Institute
Richmond, Virginia
Puget Sound Cancer Center
Seattle, Washington
University of Southern Florida -Moffitt Cancer Center
Tampa, Florida
Palm Beach Cancer Institute
West Palm Beach, Florida
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina
Russia5 sites
Arkhangelsk Regional Clinical Oncology Dispensary
Arkhangelsk
Blokhin Russian Oncology Research Center of Russian Academy of Medical Sciences
Moscow
Leningrad Regional Oncology Dispensary
Saint Petersburg
Russian Research Centre of Radiology and Surgery
Saint Petersburg
Stavropol Territory Clinical Oncology Dispensary
Stavropol
Hungary4 sites
Allami Egeszseguegi Koezpont
Budapest
Semmelweis Egyetem
Budapest
Radiologicke centrum Multiscan
Debrecen
Clinfan Ltd SMO, County Hospital Szekszard
Szekszárd
Czechia3 sites
Fakultni nemocnice Olomouc
Olomouc
Radiologicke centrum Multiscan, s.r.o.
Pardubice
Fakultani Nemocnice Kralavske Vinohadry
Praque
Canada2 sites
RSM Durham Regional Cancer Center - Lakeridge Health
Oshawa, Ontario
St. Joseph's Health Centre
Toronto, Ontario
About this study
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
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.
- Conditions
- Breast Cancer, Estrogen Receptor-Positive Breast Cancer, Breast Cancer, Estrogen Receptor-Positive, ER+ Breast Cancer
- Being tested
- entinostat, exemestane, Placebo
- Keywords
- Breast Neoplasms, Breast Tumor, Mammary Neoplasms
- Medical subject headings
- Breast Neoplasms, Mammary Neoplasms, Animal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
entinostatDrug
Also called SNDX-275
Entinostat 5 mg tablet orally once per week
exemestaneDrug
Also called Aromasin®
Exemestane 25 mg tablet orally once daily
PlaceboDrug
Placebo-matching entinostat tablet orally once per week
| Study group | Role | What they receive |
|---|---|---|
| Exemestane 25 mg + Entinostat 5 mg | Experimental | 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. Receives: Drug: entinostat; Drug: exemestane |
| Exemestane 25 mg + Placebo | Placebo comparator | 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. Receives: Drug: exemestane; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2008 (estimated)
- Study start13 Jun 2008
- Primary completion29 Jan 2011
- Study completion26 Nov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Denise Yardley, MD, Principal investigator, Sarah Cannon Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00676663
- Sponsor's protocol ID
- SNDX-275-0301
- Other IDs
- 2009-012623-28, 2009
- Acronym
- ENCORE301
- Status last verified
- Apr 2022
- First submitted
- 9 May 2008
- Last updated
- 11 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 23650416
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00676663
- Acronym / sponsor ID
- ENCORE301 / SNDX-275-0301
- Conditions
- Breast Cancer, Estrogen Receptor-Positive Breast Cancer, Breast Cancer, Estrogen Receptor-Positive, ER+ Breast Cancer
- Keywords
- Breast Neoplasms, Breast Tumor, Mammary Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2008 (actual)
- Primary completion
- 29 Jan 2011 (actual)
- Study completion
- 26 Nov 2012 (actual)
- First posted
- 13 May 2008 (estimated)
- Results
- Posted 24 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exemestane 25 mg + Entinostat 5 mg | Experimental | Drug: entinostat, Drug: exemestaneExemestane (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. |
| Exemestane 25 mg + Placebo | Placebo comparator | Drug: exemestane, Drug: PlaceboExemestane (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| entinostatAlso: SNDX-275Entinostat 5 mg tablet orally once per week | Drug | Exemestane 25 mg + Entinostat 5 mg |
| exemestaneAlso: Aromasin®Exemestane 25 mg tablet orally once daily | Drug | Exemestane 25 mg + Entinostat 5 mg, Exemestane 25 mg + Placebo |
| PlaceboPlacebo-matching entinostat tablet orally once per week | Drug | Exemestane 25 mg + Placebo |
Primary outcome
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.
3 secondary outcomes
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23650416Yardley 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.
Related trials for Breast Cancer
Not yet recruiting
Effect of a Health Belief Model Based Digital Nudge Intervention on Breast Cancer Screening
Breast Cancer Screening, Breast Cancer Awareness
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruitingPhase 2
Low-Dose Apatinib Plus Chemotherapy in ADC-Pretreated HER2-Positive and HER2-Low Advanced Breast Cancer
Breast Neoplasms, Advanced Breast Cancer
RecruitingPhase 3
ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer
Breast Neoplasms
Active, not recruitingPhase 2
Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases
Breast Cancer Stage IV
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denise Yardley, MD principal investigator
Sarah Cannon Cancer Center
38 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing entinostat and exemestane in people with Breast Cancer and Estrogen Receptor-Positive Breast Cancer, run by Syndax Pharmaceuticals at 38 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Russia, Hungary, Czechia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00676663, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2022.