AzTrials
AzTrials

Anatomic Stage III Breast Cancer AJCC v8Phase 3NCT02115282

Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic

A Phase 3 study testing Biospecimen Collection, Computed Tomography and Entinostat in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 653 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or another place in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Entinostat
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
608 participants
Where
653 sitesin 2 countries
Study dates
29 Mar 2014to 2 Jun 2027
Phase
Phase 3

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Estrogen receptor (ER) and/or progesterone receptor (PR) positive histologically confirmed adenocarcinoma of the breast with staining of >= 1% cells will be considered positive; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
  • Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
  • Patients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is not possible; lesions must be evaluated =< 4 weeks prior to study randomization; diagnostic-quality computed tomography (CT) scans with both oral and intravenous (IV) contrast are the expected radiologic method, unless an alternative is approved
  • NOTE: Where baseline imaging has already been performed =< 6 weeks prior to study randomization, repeat imaging may not be required
  • NOTE: As of October 16, 2016, accrual of new patients having non-measurable disease has stopped; the planned accrual for this target population has been reached
  • Pre/peri- and postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:
Show all 42Show fewer
  • Age >= 55 years and one year or more of amenorrhea
  • Age < 55 years and one year or more of amenorrhea, with estradiol < 20 pg/ml
  • Age < 55 with prior hysterectomy but intact ovaries, with estradiol < 20 pg/ml
  • Prior bilateral oophorectomy
  • NOTE: Women who do not fit the criteria for being postmenopausal as above are deemed pre-or peri-menopausal; pre/perimenopausal women and all men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; pre/perimenopausal women must have commenced treatment with LHRH agonist at least 4 weeks prior to randomization; if patients have received alternative LHRH agonist prior to study entry, they must switch to goserelin for the duration of the trial
  • Sexually active males and pre/perimenopausal women must agree to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 3 months after discontinuation of therapy
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study =< 2 weeks prior to randomization
  • A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients must not have known central nervous system metastasis or a history of central nervous system (CNS) metastases; patients with leptomeningeal disease are not eligible
  • Patients must be disease-free of prior invasive malignancies for > 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer
  • Patients must meet at least one of the following criteria:
  • Disease progression any time after non-steroidal AI use in the advanced disease setting
  • Relapse while on or within =< 12 months of end of adjuvant non-steroidal AI therapy with or without prior endocrine therapy for advanced disease
  • NOTE: In either setting, treatment with any prior endocrine therapy must be completed >= 2 weeks prior to cycle 1 day 1 (C1D1) of study treatment with the exception of exemestane which is permitted in the advanced disease setting within =< 4 weeks immediately prior to C1D1; prior adjuvant exemestane is allowed if the disease free interval is > 12 months from the discontinuation of exemestane; prior faslodex, everolimus, palbociclib or other cyclin-dependent kinase (CDK) inhibitor (e.g. ribociclib, abemaciclib) use are allowed and must have been completed >= 2 weeks prior to C1D1; failure to adhere to this washout guideline will result in a protocol violation
  • Patients may have received only one prior chemotherapy regimen for metastatic disease provided treatment was completed >= 3 weeks prior to randomization
  • Patients may be treated with bone modifying agents such as bisphosphonates or RANK-ligand agents (e.g. denosumab) per American Society of Clinical Oncology (ASCO) guidelines; whenever possible, patients requiring bone modifying agents should start treatment >= 7 days prior to study therapy and should continue the same agent throughout study unless clinically compelled to change
  • Prior radiotherapy must in general have been completed >= 2 weeks prior to randomization and patients must have recovered from the toxicity of the radiation
  • NOTE: Patients may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as sites of measurable or non-measurable disease outside the radiation therapy port are available to follow
  • Patients must NOT receive concurrent anti-cancer therapy or investigational agent unless specified in protocol
  • Patients must NOT be receiving valproic acid, an histone deacetylase (HDAC) inhibitor, and may not have previously received any HDAC inhibitor prior to enrollment (e.g. valproic acid, entinostat, vorinostat) unless discussed with the study chair; patients must not have received prior HDAC therapy for the treatment of their malignancy
  • Patients must have no known allergies to exemestane, entinostat, or medications that have a benzamide structure (e.g., tiapride, remoxipride, clebropride)
  • Patients must NOT suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities; this includes uncontrolled intercurrent illness including, but not limited to ongoing or active infection
  • Patients must have recovered from all clinically relevant adverse events to grade 1 or baseline due to previous agents administered (except alopecia)
  • Patients must have adequate hematologic, liver and renal function =< 28 days prior to randomization
  • NOTE: It is preferred that laboratory values for eligibility be assessed after the last dose of prior treatment, especially in cases where most-recent treatment prior to study entry is chemotherapy
  • Hemoglobin (HgB) >= 9.0 g/dL (=< 28 days prior to randomization)
  • Platelet count >= 100,000/mcL (=< 28 days prior to randomization)
  • Absolute neutrophil count >= 1,500/mcL (=< 28 days prior to randomization)
  • Creatinine =< 2.0 mg/dL (=< 28 days prior to randomization)
  • Total bilirubin < 1.5 x institutional upper limit of normal (=< 3 mg/dL in case of Gilbert's syndrome) (=< 28 days prior to randomization)
  • Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) =< 2.5 x institutional upper limit normal (=< 28 days prior to randomization)
  • Known human immunodeficiency virus (HIV)-positive patients should have a cluster of differentiation (CD)4 count > 250/mm^3
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must have a life expectancy >= 12 weeks
  • Patients must be able to swallow tablets

Who cannot join

None listed.

Trial locations and contacts

653 sites in 2 countries.

301 sites in 2 countries

United States300 sites

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Hendrick Medical Center

    Abilene, Texas, 79601

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Presbyterian Kaseman Hospital

    Albuquerque, New Mexico, 87110

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Luminis Health Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Hope Women's Cancer Centers-Asheville

    Asheville, North Carolina, 28816

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Hematology Oncology Associates of Central New York-Auburn

    Auburn, New York, 13021

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Hematology/Oncology Clinic PLLC

    Baton Rouge, Louisiana, 70809

  • Louisiana Hematology Oncology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Ochsner Health Center-Summa

    Baton Rouge, Louisiana, 70809

  • Medical Center of Baton Rouge

    Baton Rouge, Louisiana, 70816

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • Beverly Hospital

    Beverly, Massachusetts, 01915

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • OSF Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Toledo Clinic Cancer Centers-Bowling Green

    Bowling Green, Ohio, 43402

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Kings County Hospital

    Brooklyn, New York, 11203

  • State University of New York Downstate Medical Center

    Brooklyn, New York, 11203

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Saint Anne Hospital

    Burien, Washington, 98166

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Cone Health Cancer Center at Alamance Regional

    Burlington, North Carolina, 27215

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Hematology Oncology Associates of CNY at Camillus

    Camillus, New York, 13031

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • AtlantiCare Health Park-Cape May Court House

    Cape May Court House, New Jersey, 08210

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • IU Health North Hospital

    Carmel, Indiana, 46032

  • Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Swedish Covenant Hospital

    Chicago, Illinois, 60625

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Weiss Memorial Hospital

    Chicago, Illinois, 60640

  • UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Enloe Medical Center

    Chico, California, 95926

  • Adventist Health Cancer Care Center Chico

    Chico, California, 95973

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • Oncology Hematology Care Inc-Eden Park

    Cincinnati, Ohio, 45202

  • Oncology Hematology Care Inc-Mercy West

    Cincinnati, Ohio, 45211

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Anderson

    Cincinnati, Ohio, 45230

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • Oncology Hematology Care Inc-Blue Ash

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Community Cancer Institute

    Clovis, California, 93611

  • University Oncology Associates

    Clovis, California, 93611

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Baptist Memorial Hospital and Cancer Center-Golden Triangle

    Columbus, Mississippi, 39705

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Baptist Health Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Mary Bird Perkins Cancer Center - Covington

    Covington, Louisiana, 70433

  • Northshore Oncology Associates-Covington

    Covington, Louisiana, 70433

  • Oncology Hematology Care Inc-Crestview

    Crestview Hills, Kentucky, 41017

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UPMC Western Maryland

    Cumberland, Maryland, 21502

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • MercyOne Genesis Davenport Medical Center

    Davenport, Iowa, 52803

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Delaware Radiation Oncology

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Rose Medical Center

    Denver, Colorado, 80220

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Bayhealth Hospital Kent Campus

    Dover, Delaware, 19901

  • Wentworth-Douglass Hospital

    Dover, New Hampshire, 03820

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • University of Maryland Shore Medical Center at Easton

    Easton, Maryland, 21601

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Saint Elizabeth Healthcare Edgewood

    Edgewood, Kentucky, 41017

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • AtlantiCare Surgery Center

    Egg Harbor, New Jersey, 08234

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Texas Tech University Health Sciences Center-El Paso

    El Paso, Texas, 79905

  • Baptist Health Hardin

    Elizabethtown, Kentucky, 42701

  • Ascension Alexian Brothers - Elk Grove Village

    Elk Grove Village, Illinois, 60007

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • Arnot Ogden Medical Center/Falck Cancer Center

    Elmira, New York, 14905

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Saint Francis Hospital

    Evanston, Illinois, 60202

  • Oncology Hematology Care Inc-Healthplex

    Fairfield, Ohio, 45014

  • Saint Anne's Hospital

    Fall River, Massachusetts, 02721

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • IU Health Central Indiana Cancer Centers-Fishers

    Fishers, Indiana, 46037

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UI Healthcare Mission Cancer and Blood - Fort Dodge

    Fort Dodge, Iowa, 50501

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Saint Elizabeth Healthcare Fort Thomas

    Fort Thomas, Kentucky, 41075

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Hematology Oncology Associates of Fredericksburg Inc

    Fredericksburg, Virginia, 22408

  • Freeport Memorial Hospital/Leonard C Ferguson Cancer Center

    Freeport, Illinois, 61032

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Saint Catherine Hospital

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Addison Gilbert Hospital

    Gloucester, Massachusetts, 01930

  • Mountain Blue Cancer Care Center

    Golden, Colorado, 80401

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Saint Rose Ambulatory and Surgery Center

    Great Bend, Kansas, 67530

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Banner North Colorado Medical Center

    Greeley, Colorado, 80631

  • Bellin Memorial Hospital

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Rocky Mountain Cancer Centers-Greenwood Village

    Greenwood Village, Colorado, 80111

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Baptist Cancer Center-Grenada

    Grenada, Mississippi, 38901

  • William Beaumont Hospital-Grosse Pointe

    Grosse Pointe, Michigan, 48230

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • The Cancer Institute of New Jersey Hamilton

    Hamilton, New Jersey, 08690

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Hattiesburg Clinic - Hematology/Oncology Clinic

    Hattiesburg, Mississippi, 39401

  • Forrest General Hospital / Cancer Center

    Hattiesburg, Mississippi, 39404

  • HaysMed

    Hays, Kansas, 67601

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • Mary Bird Perkins Cancer Center - Houma

    Houma, Louisiana, 70360

  • Oncology Center of The South Incorporated

    Houma, Louisiana, 70360

  • Edwards Comprehensive Cancer Center

    Huntington, West Virginia, 25701

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Centerpoint Medical Center LLC

    Independence, Missouri, 64057

  • Cleveland Clinic Cancer Center Independence

    Independence, Ohio, 44131

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • IU Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • Sidney and Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • IU Health Central Indiana Cancer Centers-East

    Indianapolis, Indiana, 46219

  • Franciscan Health Indianapolis

    Indianapolis, Indiana, 46237

  • Springmill Medical Center

    Indianapolis, Indiana, 46290

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Jackson-Madison County General Hospital

    Jackson, Tennessee, 38301

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

Other trials in United States

South Africa1 site

  • University Of Pretoria

    Pretoria, 0002

Other trials in South Africa

About this study

Official title: A Randomized Phase III Trial of Endocrine Therapy Plus Entinostat/Placebo in Patients With Hormone Receptor-Positive Advanced Breast Cancer

This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or another place in the body (metastatic). Estrogen can cause the growth of breast cancer cells. Endocrine therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether exemestane is more effective with or without entinostat in treating breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate whether the addition of entinostat to endocrine therapy (exemestane) improves progression-free survival (PFS) and/or overall survival (OS) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have previously progressed on a non-steroidal aromatase inhibitor (Al).

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of entinostat in combination with exemestane, and to compare the safety profile to that of endocrine therapy with placebo.

II. To evaluate the objective response rate of exemestane in combination with entinostat or placebo.

III. To evaluate whether the efficacy of exemestane with entinostat varies with changes in acetylation status in peripheral blood mononuclear cells (PBMCs).

IV. To evaluate the time to treatment deterioration (as defined by decrease in health-related quality of life [HRQL], progression, death) of exemestane + entinostat versus exemestane + placebo arms.

  1. To evaluate the differences in overall health-related quality of life (HRQL) between the exemestane + entinostat versus exemestane + placebo arms.

VI. To evaluate the difference with respect to specific symptoms that are associated with entinostat, i.e., fatigue, nausea, anorexia and diarrhea, between the exemestane + entinostat versus exemestane + placebo arms.

VII. To measure adherence to protocol therapy. VIII. To evaluate the pharmacokinetics of entinostat in patients with advanced breast cancer.

IX. To evaluate what, if any, patient variables alter the pharmacokinetic profile of entinostat in patients with advanced breast cancer.

EXPLORATORY OBJECTIVES:

  1. To collect archival tumor samples and germline deoxyribonucleic acid (DNA) to explore other potential biomarkers of therapeutic efficacy.

II. To collect patient ratings of adverse events (AEs) using select patient-reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items to evaluate the psychometric properties of PRO-CTCAE items and explore the incorporation of PRO-CTCAE items into a phase III double-blind placebo-controlled trial.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive exemestane orally (PO) once daily (QD) on days 1-28 and entinostat PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline.

ARM B: Patients receive exemestane as in Arm A and placebo PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline.

In both arms, pre/perimenopausal female patients and all male patients also receive goserelin acetate subcutaneously (SC) on day 1.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Being tested
Biospecimen Collection, Computed Tomography, Entinostat, Exemestane, Goserelin
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood and archived tissue samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • EntinostatDrug

    Also called HDAC inhibitor SNDX-275, MS 27-275, MS 275, MS-275

    Given PO

  • ExemestaneDrug

    Also called Aromasin, FCE-24304

    Given PO

  • GoserelinDrug

    Also called ICI-118630

    Given PO

  • Goserelin AcetateDrug

    Also called ZDX, Zoladex

    Given SC

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Placebo AdministrationOther

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT02115282
Study groupRoleWhat they receive
Arm A (exemestane, entinostat)ExperimentalPatients receive exemestane PO QD on days 1-28 and entinostat PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline. Pre/perimenopausal female patients and all male patients also receive goserelin acetate SC on day 1.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Entinostat; Drug: Exemestane; Drug: Goserelin; Drug: Goserelin Acetate; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment
Arm B (exemestane, placebo)Placebo comparatorPatients receive exemestane as in Arm A and placebo PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline. Pre/perimenopausal female patients and all male patients also receive goserelin acetate SC on day 1.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Exemestane; Drug: Goserelin; Drug: Goserelin Acetate; Procedure: Magnetic Resonance Imaging; Other: Placebo Administration; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Progression-free survival (PFS) was defined to be time from randomization to the earliest documented disease progression as defined by the RECIST criteria, new primary breast cancer, or death without progression. Disease assessment was to continue until disease progression, even after non-protocol anti-cancer therapy was started. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of progression, regardless of whether non-protocol anti-cancer therapy was started or not. Disease progression was based on central review, and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. In addition, the appearance of one or more new lesions was also considered progression. Kaplan-Meier method was used to estimate PFS rate.

    Measured: Assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression

  2. Overall Survival (OS)

    Overall survival (OS) was defined to be time from randomization to death from any cause. Cases who were still alive were censored at the date last known alive.

    Measured: Assessed every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until death

Secondary outcomes (7)

  1. Objective Response Rate (ORR)

    Objective response rate was defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses were evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR was defined as disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).

    Measured: Assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression

  2. Time-to-treatment Deterioration (TTD)

    Time-to-treatment deterioration (TTD) was defined as time from randomization to disease progression or death or worsening of symptoms, whichever occurred first. Disease progression was assessed per RECIST v1.1. Symptoms deterioration was measured by 6 items (GP1, GP2, GP4, GF7, B1, P2, scored 0-24) from the 8-item FACT-Breast Symptom Index (FBSI). Symptom deterioration was defined as two consecutive available decreases of at least 3 points from baseline using the 6-item FBSI in this trial, and the second visit time was used as the time of symptom deterioration in this case, unless it was the final score, for which one decrease was sufficient. Kaplan-Meier method was used to estimate the median TTD and TTD rate at a certain time point. Symptoms were assessed every cycle for the first six months after randomization, every two cycles between 6 months and 1 year. It then were assessed based on the same schedule for tumor assessments until disease progression as specified below.

    Measured: Disease assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression

  3. Lysine Acetylation Change in CD45 Blood Mononuclear Cells Between C1D1 and C1D15 and PFS in Patients on Arm A

    Peripheral blood samples (PBMCs) were collected prior to therapy and on Days 8 and 15 of cycle 1, for assessment of lysine acetylation, using an assay developed by the Trepel Laboratory, NCI/NIH. CD45 blood mononuclear cells were measured. Patients with lysine acetylation change of 1.5 folds or higher were compared to patients with lysine acetylation change of less than 1.5 folds.

    Measured: Disease assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression

  4. Patient-reported Health-related Quality of Life

    Health-related quality of life (HRQL) was measured using Functional Assessment of Cancer Therapy - General (FACT-G). The primary endpoint for HRQL was the FACT-G Trial Outcome Index (TOI) which was an aggregate score of 5 items from the FACT-G-Physical subscale (GP2, GP3, GP4, GP6, and GP7) and 6 items from the FACT-G-Functional subscale (GF1, GF2, GF3, GF4, GF6, and GF7). All items were rated on a 5-point Likert scale from 0 to 4. FACT-G TOI subscale score was calculated based on the scoring manual, subscale score ranges from 0 to 44, and higher scores indicate better quality of life. The primary comparison of HRQL between treatment arms was based on the end of cycle 3 assessment.

    Measured: Assessed at baseline and end of cycle 3

  5. Patient-reported Diarrhea

    Diarrhea was measured by Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea (FACIT-Diarrhea) subscale form, which had 11 items, all items were rated on a 5-point Likert scale from 0 to 4. FACIT-Diarrhea subscale score was calculated based on the scoring manual, subscale score ranges from 0 to 44, and higher score indicates less diarrhea. The primary comparison of patient-reported diarrhea between treatment arms was based on the end of cycle 3 assessment.

    Measured: Assessed at baseline and end of cycle 3

  6. Patient-reported Fatigue

    Fatigue was measured by PROMIS Fatigue short form, it had 7 items and all items were rated on a 5-point Likert scale from 1 to 5. The PROMIS Fatigue total score and T score were calculated based on the scoring manual. The total score ranges from 7 to 35, the T score ranges from 29.4 to 83.2, higher scores indicate more fatigue. The PROMIS Fatigue T score was used for arm comparison. The primary comparison of patient-reported fatigue between treatment arms was based on the end of cycle 3 assessment.

    Measured: Assessed at baseline and end of cycle 3

  7. Patient-reported Nausea and Anorexia

    Nausea and anorexia were measured by The Functional Assessment of Anorexia/Cachexia Treatment (FAACT)-additional concerns, which had 12 items, all items were rated on a 5-point Likert scale from 0 to 4. FAACT-additional concerns subscale score was calculated based on scoring manual. Subscale score ranges from 0 to 48, and higher scores indicate less nausea and anorexia. The primary comparison of patient-reported nausea and anorexia between treatment arms was based on the end of cycle 3 assessment.

    Measured: Assessed at baseline and end of cycle 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2014 (estimated)
  2. Study start29 Mar 2014
  3. Primary completion5 May 2020
  4. Study completion2 Jun 2027 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
608 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02115282
Sponsor's protocol ID
NCI-2014-00746
Other IDs
NCI-2014-00746, ECOG-E2112, E2112, E2112, U10CA021115, U10CA180820, U24CA196172
Status last verified
Jun 2026
First submitted
14 Apr 2014
Last updated
22 Oct 2026
Data monitoring committee
No

Publications

  • Connolly RM, Zhao F, Miller KD, Lee MJ, Piekarz RL, Smith KL, Brown-Glaberman UA, Winn JS, Faller BA, Onitilo AA, Burkard ME, Budd GT, Levine EG, Royce ME, Kaufman PA, Thomas A, Trepel JB, Wolff AC, Sparano JA. E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2021 Oct 1;39(28):3171-3181. doi: 10.1200/JCO.21.00944. Epub 2021 Aug 6.

    PubMed 34357781

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