Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer (ExCel)

A Phase III Randomized Study of Exemestane Versus Placebo in Postmenopausal Women at Increased Risk of Developing Breast Cancer

RATIONALE: The MAP.3 study was designed to test whether hormone therapy using exemestane may prevent breast cancer by blocking the production of estrogen.

PURPOSE: The study protocol was amended in May 2011 and the current purpose of the study is to allow all study participants the opportunity to complete 5 years of exemestane.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: exemestane

Detailed Description

OBJECTIVES:

Primary

Previously: To determine if exemestane reduces the incidence of invasive breast cancer compared with placebo.

Currently: To determine the frequency of serious adverse events for post-menopausal women at high-risk of developing breast cancer who choose to receive 5 years of exemestane as preventative therapy.

Secondary

Previously: (same as is currently listed in PDQ) Currently: To address the Trial Committee and Sponsor's commitment to allow women who are randomized to the MAP.3 trial to receive 5 years of exemestane therapy.

OUTLINE: This study was a randomized, double-blind, placebo-controlled, multicentre study. Protocol-specified analyses were performed in April 2011. The results of these analyses are posted in the Results section. Following the amendment of May 2011, the study is now open-label and all eligible patients are receiving exemestane from participating sites for a total of 5 years. After exemestane is stopped, there is no further follow-up.

PROJECTED ACCRUAL:There were 4560 women from the United States, Canada, Spain and France who took part in this study.

• Study Type: Interventional
• Enrollment (Actual): 4560
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • BCCA - Cancer Centre for the Southern Interior
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario at Kingston
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Health Research Institute - General Division
    • Ottawa, Ontario, Canada, K2C 3R2
      • Meadowlands Family Health Centre
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Algoma District Cancer Program
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeast Cancer Center Health Sciences
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5S 1B2
      • Women's College Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H3X 3J4
      • CHUM - Pavillon Saint-Luc
    • Quebec City, Quebec, Canada, G1S 4L8
      • CHA-Hopital Du St-Sacrement
• France
  • Angers, France, 49933
    • CRLCC - Paul Papin
  • Brest, France, 29608
    • CHU-Hopital A. Morvan
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Limoges, France, 87042
    • CHU de Limoges - Hopital Mere Enfant
  • Montpellier, France, 34295
    • CHU - Hopital Arnaud de Villeneuve
  • Nantes, France, 44805
    • Centre Rene Gauducheau
  • Neuilly-sur-Seine, France, 92200
    • Clinique Hartmann
  • Paris, France, 75970
    • AP-HP Hopital Tenon
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Cloud, France, 92210
    • Centre René Huguenin
  • Vandoeuvre les Nancy, France, 54500
    • Centre Alexis Vautrin
  • Villejuif, France, 94805
    • Institut Gustave-Roussy
• Puerto Rico
  • Orocovis, Puerto Rico, 00720
    • Orocovis Medical Center
  • San Juan, Puerto Rico, 00920
    • Altamira Family Research Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Jefferson Clinic, P.C.
    • Birmingham, Alabama, United States, 35294-0111
      • UAB Comprehensive Cancer Center-LNB 301
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego
    • Sacramento, California, United States, 95817
      • University of California at Davis
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • University of Connecticut Health Center
    • Norwalk, Connecticut, United States, 06856
      • Whittingham Cancer Center at Norwalk Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Georgia
    • Tucker, Georgia, United States, 30084
      • Georgia Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Mercy Hospital and Medical Center
    • Chicago, Illinois, United States, 60612
      • John H. Stroger, Jr Hospital of Cook County
    • Chicago, Illinois, United States, 60637-1470
      • The University of Chicago Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Centre
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Normal, Illinois, United States, 61761
      • Mid-Illinois Hematology and Oncology Associates, Ltd.
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Centre
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7820
      • University of Kansas Medical Center
  • Maine
    • Scarborough, Maine, United States, 04074-9308
      • Maine Center for Cancer Medicine and Blood Disorders
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Suburban Hospital Cancer Program
    • Hyattsville, Maryland, United States, 20782
      • MedStar Health Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Hutzel Women's Health Specialists
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Newark, New Jersey, United States, 07107
      • University of Medicine and Dentistry of New Jersey
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati, Barrett Cancer Centre
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Abramson Cancer Center of the
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • The Memorial Hospital of Rhode Island
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Univ. of Wisconsin Center for Women's Health and
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

• At increased risk of developing breast cancer, due to at least one of the following risk factors:

  • Gail score ≥ 1.66
  • Age ≥ 60 years
  • Prior atypical ductal hyperplasia, lobular hyperplasia, or lobular carcinoma in situ on breast biopsy
  • Prior ductal carcinoma in situ (DCIS) treated with total mastectomy with or without tamoxifen (tamoxifen must have been completed ≥ 3 months prior to randomization)
• No prior DCIS treated with lumpectomy with or without radiation
• No prior invasive breast cancer
• Not BRCA1 or BRCA2 carriers

PATIENT CHARACTERISTICS:

Previous:

• 35 and over
• Female

• Postmenopausal, defined as one of the following:

  • over 50 years of age with no spontaneous menses for at least 12 months before study entry
  • 50 years of age or under with no menses (spontaneous or secondary to hysterectomy) for at least 12 months before study entry AND with follicle-stimulating hormone level within postmenopausal range
  • Underwent prior bilateral oophorectomy
• No other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 5 years
• No uncontrolled hypothyroidism or hyperthyroidism
• No major medical or psychiatric illness (including substance and alcohol abuse within the past 2 years) that would preclude study participation or compliance
• Must be accessible for treatment and follow-up
• Willing to complete quality of life questionnaires in either English or French

Current: MAP.3 participants who were randomized to the exemestane arm, are currently receiving exemestane as part of the MAP.3 study and who have not completed 5 years of exemestane.

OR MAP.3 study participants who were randomized to the placebo arm and who have either completed 5 years of study drug or who are still receiving placebo. Note: this applies only to centres that choose to allow placebo "cross-over".

PRIOR CONCURRENT THERAPY:

Previous:

• More than 3 months since prior and no concurrent hormone replacement therapies
• More than 3 months since systemic estrogenic, androgenic, or progestational agents

• More than 3 months since prior and no concurrent hormonal therapies, including, but not limited to the following:

  • Luteinizing-hormone releasing-hormone analogs (e.g., goserelin or leuprolide)
  • Progestogens (e.g., megestrol)
  • Prolactin inhibitors (e.g., bromocriptine)
  • Antiandrogens (e.g., cyproterone acetate)
  • Selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or raloxifene)
• No investigational drug within 30 days or 5 half lives prior to randomization
• No concurrent endocrine therapy
• No concurrent estrogens, androgens, or progesterones
• Concurrent low dose (≤ 100 mg/day) prophylactic aspirin allowed
• Concurrent bisphosphonates for prevention or treatment of osteoporosis allowed
• No other concurrent medications that may have an effect on study endpoints

Current: There are no prior concurrent therapy restrictions for the amended MAP.3 study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Exemestane; one 25 mg tablet daily in am	Drug: exemestane; one 25 mg tablet daily in am

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Women With Serious Adverse Events	Percentage of serious adverse events for women who choose to receive 5 years of exemestane as preventative therapy.	5 years open-label extension period
Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)	Invasive breast cancer incidence was estimated from the breast cancer-free survival (BCFS) which was calculated for all women from the day of the randomization to the earliest date of diagnosis for invasive breast cancer. Women who died from other causes were censored at the time of death. If a woman did not develop an invasive breast cancer, or died, BCFS was censored on the date of the last day the woman was known alive (LKA), which was the latest of the date of assessment. Women who had breast cancer before study entry were also censored at the time of randomization.	Over randomization period of study (median follow-up 35 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer	It was estimated from the Total Breast Cancer-Free Survival (TBCFS), which was calculated for women who developed invasive or non-invasive (DCIS) breast cancer as the time from the date of randomization to the earliest date of diagnosis for invasive or non-invasive (DCIS) breast cancer. Women who died from other causes were censored at the time of death. Women who had breast cancer before entry were censored at the time of randomization. If a woman did not develop an invasive or non-invasive (DCIS) breast cancer, or died, TBCFS will be censored on the date of last known alive.	Over randomization period of study (median follow-up 35 months)
Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events		Over randomization period of study (median follow-up 35 months)
Number of Clinical Breast Biopsies		Over randomization period of study (median follow-up 35 months)
Incidence of All Clinical Fractures		During protocol treatment over randomization period of study (up to 5 years)
Incidence of Clinically Relevant Cardiac Events	Events including myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes and all vascular deaths	During protocol treatment in randomization period (up to 5 years)
Incidences of Other Malignancies	Other malignancies includes any other malignancy which is not in breast.	Over randomization period of study (median follow-up 35 months)

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: UNICANCER; Grupo Espanol de Investigacion del Cancer de Mama
• Investigators: Study Chair: Paul E. Goss, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Richardson H, Johnston D, Pater J, Goss P. The National Cancer Institute of Canada Clinical Trials Group MAP.3 trial: an international breast cancer prevention trial. Curr Oncol. 2007 Jun;14(3):89-96. doi: 10.3747/co.2007.117.
• Goss PE, Richardson H, Chlebowski R, Johnston D, Sarto GE, Maunsell E, Ingle JN, Ales-Martinez JE. National Cancer Institute of Canada Clinical Trials Group MAP.3 Trial: evaluation of exemestane to prevent breast cancer in postmenopausal women. Clin Breast Cancer. 2007 Dec;7(11):895-900. doi: 10.3816/CBC.2007.n.057. No abstract available.
• Moy B, Richardson H, Johnston D, et al.: NCIC CTG MAP.3: enrollment and study drug adherence of ethnic minority women in a breast cancer prevention trial. [Abstract] Breast Cancer Res Treat 106 (1): A-3048, S141-2, 2007.
• Richardson H, Johnston D, Goss PE, et al.: Participant characteristics on an international NCIC CTG breast cancer prevention trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-1531, 2007.
• Goss PE, Ingle JN, Alés-Martinez J, Cheung A, Chlebowski RT, Wactawski-Wende J, McTiernan A, Robbins J, Johnson K, Martin L, Winquist E, Sarto G, Garber JE, Fabian CJ, Pujol P, Maunsell E, Farmer P, Gelmon KA, Tu D, Richardson H. Exemestane for primary prevention of breast cancer in postmenopausal women: NCIC CTG MAP.3 - A randomized placebo-controlled clinical trial. J Clin Oncol 29[suppl; abstr LBA504], 2011.
• Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A, Robbins J, Johnson KC, Martin LW, Winquist E, Sarto GE, Garber JE, Fabian CJ, Pujol P, Maunsell E, Farmer P, Gelmon KA, Tu D, Richardson H; NCIC CTG MAP.3 Study Investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. doi: 10.1056/NEJMoa1103507. Epub 2011 Jun 4. Erratum In: N Engl J Med. 2011 Oct 6;365(14):1361.
• Maunsell E, Goss PE, Chlebowski RT, Ingle JN, Ales-Martinez JE, Sarto GE, Fabian CJ, Pujol P, Ruiz A, Cooke AL, Hendrix S, Thayer DW, Rowland KM, Dube P, Spadafora S, Pruthi S, Lickley L, Ellard SL, Cheung AM, Wactawski-Wende J, Gelmon KA, Johnston D, Hiltz A, Brundage M, Pater JL, Tu D, Richardson H. Quality of life in MAP.3 (Mammary Prevention 3): a randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer. J Clin Oncol. 2014 May 10;32(14):1427-36. doi: 10.1200/JCO.2013.51.2483. Epub 2014 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2004
• Primary Completion (Actual): March 25, 2011
• Study Completion (Actual): January 22, 2018

Study Registration Dates

• First Submitted: May 14, 2004
• First Submitted That Met QC Criteria: May 14, 2004
• First Posted (Estimated): May 17, 2004

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: MAP3; CAN-NCIC-MAP3 (Registry Identifier: PDQ); PFIZER-EXEAPO-0028-150 (Other Identifier: Pfizer); CDR0000363802 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No