In English | En español
Questions About Cancer? 1-800-4-CANCER

Clinical Trials (PDQ®)

Page Options

  • Print This Page
  • Email This Document
Clinical Trial Questions?
Get Help:
1-800-4-CANCER
LiveHelp online chat

Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive18 and overNCINCI-2014-00746
ECOG-E2112, E2112, U10CA021115, U10CA180820, NCT02115282

Trial Description

Summary

This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating postmenopausal patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes or another place in the body. 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.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate whether the addition of entinostat to endocrine therapy (exemestane) improves progression-free survival (PFS) and/or overall survival (OS) in postmenopausal 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:

I. 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.

V. 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.

TERTIARY OBJECTIVES:

I. 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive exemestane as in Arm A and placebo PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

In both arms, 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.

Eligibility Criteria

Inclusion Criteria:

  • 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
  • Postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:
  • 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: Men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; LHRH agonist use is not permitted for female patients
  • Sexually active males must be strongly advised 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
  • 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 after non-steroidal aromatase inhibitor (AI) use in the metastatic setting
  • Relapse while on or within =< 12 months of end of adjuvant non-steroidal AI therapy with no prior or =< 4 weeks of endocrine therapy for metastatic disease
  • NOTE: Prior exemestane or fulvestrant is not allowed; prior everolimus therapy is allowed and must have been completed 2 weeks prior to study entry; other prior endocrine therapy for metastatic disease is allowed (e.g. tamoxifen) and must have been completed 2 weeks prior to study entry
  • Patients may have received 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 receptor activator of nuclear factor kappa-B (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)
  • Patients must have no known allergies to imidazole drugs (e.g. clotrimazole, ketoconazole, miconazole, econazole, sulconazole, ticonazole, or terconazole), exemestane or entinostat
  • 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
  • Platelet count >= 100,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Creatinine =< 2.0 mg/dL
  • Total bilirubin < 1.5 x institutional upper limit of normal (=< 3 mg/dL in case of Gilbert's syndrome)
  • Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) =< 2.5 x institutional upper limit normal
  • 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Roisin ConnollyPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 UAB Comprehensive Cancer Center
 Carla I. Falkson Ph: 205-934-0309
California
  Paradise
 Feather River Hospital Cancer Center
 Sam Mazj Ph: 530-876-7995
  Email: haleew@ah.org
  Saint Helena
 Saint Helena Hospital
 Gregory B Smith Ph: 707-967-3698
Connecticut
  New Britain
 George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
 Brian J Byrne Ph: 860-224-5660
Georgia
  Atlanta
 Georgia Cancer Center for Excellence at Grady Memorial Hospital
 Ruth M. O'Regan Ph: 404-778-1868
 Winship Cancer Institute of Emory University
 Ruth M. O'Regan Ph: 404-778-1868
 Ruth M. O'Regan Ph: 404-778-1868
Idaho
  Boise
 Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
 Christopher M Reynolds Ph: 734-712-3456
Illinois
  Joliet
 Joliet Oncology-Hematology Associates, Limited - West
 Kulumani M Sivarajan Ph: 815-730-3098
  Email: maureenc@jolietoncology.com
  Mount Vernon
 Good Samaritan Regional Health Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
Indiana
  Indianapolis
 Indiana University Melvin and Bren Simon Cancer Center
 Kathy Miller Ph: 317-274-2552
  Muncie
 Cancer Center at Ball Memorial Hospital
 Michael J Williamson Ph: 765-751-5850
  Email: alpatterson@medicalconsultantspc.com
Iowa
  Ames
 McFarland Clinic, PC
 Joseph James Merchant Ph: 515-239-2621
 William R. Bliss Cancer Center at Mary Greeley Medical Center
 Joseph James Merchant Ph: 515-239-2621
  Boone
 McFarland Clinic PC-Boone
 Joseph James Merchant Ph: 515-239-2621
  Cedar Rapids
 Cedar Rapids Oncology Associates
 Deborah W Wilbur Ph: 319-363-2690
  Davenport
 Genesis Regional Cancer Center at Genesis Medical Center
 George Kovach Ph: 800-446-6088
  Email: werners@genesishealth.com
  Fort Dodge
 Trinity Regional Medical Center
 Joseph James Merchant Ph: 515-239-2621
  Jefferson
 McFarland Clinic PC-Jefferson
 Joseph James Merchant Ph: 515-239-2621
  Marshalltown
 McFarland Clinic PC-Marshalltown
 Joseph James Merchant Ph: 515-239-2621
Maine
  Augusta
 Harold Alfond Center for Cancer Care
 Thomas Henry Openshaw Ph: 207-973-4274
  York
 York Hospital's Oncology Treatment Center
 Jonathan D Eneman Ph: 207-351-3777
Maryland
  Baltimore
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Roisin M Connolly Ph: 410-955-8804
  Email: jhcccro@jhmi.edu
  Easton
 Shore Regional Cancer Center at Memorial Hospital - Easton
 Mary S. DeShields Ph: 410-820-6800ext108
  Email: srichter@shorehealth.org
Michigan
  Adrian
 Hickman Cancer Center at Bixby Medical Center
 Rex B Mowat Ph: 517-265-0116
  Ann Arbor
 Saint Joseph Mercy Cancer Center
 Christopher M Reynolds Ph: 734-712-3456
  Dearborn
 Oakwood Cancer Center at Oakwood Hospital and Medical Center
 Christopher M Reynolds Ph: 734-712-3456
  Flint
 Genesys Hurley Cancer Institute
 Christopher M Reynolds Ph: 734-712-3456
 Hurley Medical Center
 Christopher M Reynolds Ph: 734-712-3456
  Port Huron
 Mercy Regional Cancer Center at Mercy Hospital
 Christopher M Reynolds Ph: 734-712-3456
  Saginaw
 Seton Cancer Institute at Saint Mary's - Saginaw
 Christopher M Reynolds Ph: 734-712-3456
Missouri
  Branson
 Skaggs Cancer Center at Skaggs Regional Medical Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
  Cape Girardeau
 Southeast Cancer Center
 Alan Philip Lyss Ph: 800-392-0936
  Saint Louis
 David C. Pratt Cancer Center at St. John's Mercy
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
 Mercy Clinic St. Louis Cancer and Breast Institute
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
  Springfield
 Hulston Cancer Center at Cox Medical Center South
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
 St. John's Regional Health Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
New Jersey
  Hackensack
 CCOP - Northern New Jersey
 Donna T McNamara Ph: 201-996-2879
  Vineland
 Frank and Edith Scarpa Regional Cancer Pavillion at South Jersey Healthcare
 Carl J. Minniti Ph: 856-641-7933
New Mexico
  Albuquerque
 Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital
 Ursa A Brown-Glaberman Ph: 505-272-6972
 University of New Mexico Cancer Center
 Ursa A Brown-Glaberman Ph: 505-272-6972
New York
  Bronx
 Jack D. Weiler Hospital at Montefiore Medical Center - East Campus
 Christine M. Pellegrino Ph: 718-904-2730
  Email: aecc@aecom.yu.edu
 Montefiore Medical Center
 Christine M. Pellegrino Ph: 718-904-2730
  Email: aecc@aecom.yu.edu
  White Plains
 Dickstein Cancer Treatment Center at White Plains Hospital Center
 Karen B Green Ph: 914-681-2290
North Carolina
  Hendersonville
 Comprehensive Cancer Center at Pardee Hospital
 James E. Radford Ph: 828-696-4716
 Hendersonville Hematology and Oncology
 James E. Radford Ph: 828-696-4716
Ohio
  Bowling Green
 Wood County Oncology Center
 Rex B Mowat Ph: 517-265-0116
  Maumee
 Northwest Ohio Oncology Center
 Rex B Mowat Ph: 517-265-0116
  Oregon
 St. Charles Mercy Hospital
 Rex B Mowat Ph: 517-265-0116
 Toledo Clinic - Oregon
 Rex B Mowat Ph: 517-265-0116
  Toledo
 CCOP - Toledo Community Hospital
 Rex B Mowat Ph: 517-265-0116
 St. Anne Mercy Hospital
 Rex B Mowat Ph: 517-265-0116
Oklahoma
  Lawton
 Cancer Centers of Southwest Oklahoma, LLC - Lawton
 Nadim F. Nimeh Ph: 877-231-4440
Pennsylvania
  West Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Terrence P. Cescon Ph: 610-988-9323
  Williamsport
 Susquehanna Cancer Center at Divine Providence Hospital
 Warren L Robinson Ph: 800-598-4282
South Dakota
  Rapid City
 Rapid City Regional Hospital
 Mark T Schroeder Ph: 605-716-3982
  Email: research@rcrh.org
Wisconsin
  Green Bay
 Bellin Memorial Hospital
 Patrick J Mansky Ph: 920-435-8326

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT02115282
ClinicalTrials.gov processed this data on July 01, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

Back to TopBack to Top