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

Breast Cancer Clinical Trial

— ExCel  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00083174
• Other study ID #: MAP3
• Secondary ID: CAN-NCIC-MAP3PFI
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2004
• Est. completion date: January 22, 2018

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00304486

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4560
• Est. completion date: January 22, 2018
• Est. primary completion date: March 25, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 35 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• exemestane
one 25 mg tablet daily in am

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	CHUM - Pavillon Saint-Luc	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Meadowlands Family Health Centre	Ottawa	Ontario
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Women's College Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	CRLCC - Paul Papin	Angers
France	CHU-Hopital A. Morvan	Brest
France	Centre Francois Baclesse	Caen
France	CHU de Limoges - Hopital Mere Enfant	Limoges
France	CHU - Hopital Arnaud de Villeneuve	Montpellier
France	Centre Rene Gauducheau	Nantes
France	Clinique Hartmann	Neuilly-sur-Seine
France	AP-HP Hopital Tenon	Paris
France	Institut Jean Godinot	Reims
France	Centre Henri Becquerel	Rouen
France	Centre Rene Huguenin	Saint Cloud
France	Centre Alexis Vautrin	Vandoeuvre les Nancy
France	Institut Gustave-Roussy	Villejuif
Puerto Rico	Orocovis Medical Center	Orocovis
Puerto Rico	Altamira Family Research Center	San Juan
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Suburban Hospital Cancer Program	Bethesda	Maryland
United States	Jefferson Clinic, P.C.	Birmingham	Alabama
United States	UAB Comprehensive Cancer Center-LNB 301	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	John H. Stroger, Jr Hospital of Cook County	Chicago	Illinois
United States	Mercy Hospital and Medical Center	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati, Barrett Cancer Centre	Cincinnati	Ohio
United States	Hutzel Women's Health Specialists	Detroit	Michigan
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	MedStar Health Research Institute	Hyattsville	Maryland
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	University of California, San Diego	La Jolla	California
United States	Univ. of Wisconsin Center for Women's Health and	Madison	Wisconsin
United States	Loyola University Medical Centre	Maywood	Illinois
United States	University of Miami School of Medicine	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Trinity Medical Center	Moline	Illinois
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Mid-Illinois Hematology and Oncology Associates, Ltd.	Normal	Illinois
United States	Whittingham Cancer Center at Norwalk Hospital	Norwalk	Connecticut
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	The Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Abramson Cancer Center of the	Philadelphia	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	University of California at Davis	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Maine Center for Cancer Medicine and Blood Disorders	Scarborough	Maine
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Los Angeles Biomedical Research Institute	Torrance	California
United States	Georgia Cancer Specialists	Tucker	Georgia
United States	Carle Cancer Centre	Urbana	Illinois
United States	The George Washington University	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Grupo Espanol de Investigacion del Cancer de Mama, UNICANCER

Countries where clinical trial is conducted

United States,  Canada,  France,  Puerto Rico, 

References & Publications (6)

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 pr

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 — View Citation

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 Breas — View Citation

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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events		Over randomization period of study (median follow-up 35 months)
Secondary	Number of Clinical Breast Biopsies		Over randomization period of study (median follow-up 35 months)
Secondary	Incidence of All Clinical Fractures		During protocol treatment over randomization period of study (up to 5 years)
Secondary	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)
Secondary	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)