Clinical trial NCT00083174: Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer
Official title: A Phase III Randomized Study of Exemestane Versus Placebo in Postmenopausal Women at Increased Risk of Developing Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Grupo Espanol de Investigacion del Cancer de Mama
name: UNICANCER
First posted: 2004-05-17
Enrollment: 4560
Sex: FEMALE
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Percentage of Women With Serious Adverse Events
timeFrame: 5 years open-label extension period
measure: Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)
timeFrame: Over randomization period of study (median follow-up 35 months)
Secondary outcomes:
measure: Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer
timeFrame: Over randomization period of study (median follow-up 35 months)
measure: Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events
timeFrame: Over randomization period of study (median follow-up 35 months)
measure: Number of Clinical Breast Biopsies
timeFrame: Over randomization period of study (median follow-up 35 months)
measure: Incidence of All Clinical Fractures
timeFrame: During protocol treatment over randomization period of study (up to 5 years)
measure: Incidence of Clinically Relevant Cardiac Events
timeFrame: During protocol treatment in randomization period (up to 5 years)
measure: Incidences of Other Malignancies
timeFrame: Over randomization period of study (median follow-up 35 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Jefferson Clinic, P.C.
state: Alabama
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center-LNB 301
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Sacramento
country: United States
facility: University of California at Davis
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Norwalk
country: United States
facility: Whittingham Cancer Center at Norwalk Hospital
state: Connecticut
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Tucker
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: John H. Stroger, Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Mercy Hospital and Medical Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Centre
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center
state: Illinois
city: Normal
country: United States
facility: Mid-Illinois Hematology and Oncology Associates, Ltd.
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Centre
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Bethesda
country: United States
facility: Suburban Hospital Cancer Program
state: Maryland
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Hutzel Women's Health Specialists
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Barrett Cancer Centre
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the
state: Pennsylvania
city: Pawtucket
country: United States
facility: The Memorial Hospital of Rhode Island
state: Rhode Island
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: Univ. of Wisconsin Center for Women's Health and
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute - General Division
state: Ontario
city: Ottawa
country: Canada
facility: Meadowlands Family Health Centre
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Center Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Pavillon Saint-Luc
state: Quebec
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
city: Angers
country: France
facility: CRLCC - Paul Papin
city: Brest
country: France
facility: CHU-Hopital A. Morvan
city: Caen
country: France
facility: Centre Francois Baclesse
city: Limoges
country: France
facility: CHU de Limoges - Hopital Mere Enfant
city: Montpellier
country: France
facility: CHU - Hopital Arnaud de Villeneuve
city: Nantes
country: France
facility: Centre Rene Gauducheau
city: Neuilly-sur-Seine
country: France
facility: Clinique Hartmann
city: Paris
country: France
facility: AP-HP Hopital Tenon
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Vandoeuvre les Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave-Roussy
city: Orocovis
country: Puerto Rico
facility: Orocovis Medical Center
city: San Juan
country: Puerto Rico
facility: Altamira Family Research Center
Study officials:
affiliation: Massachusetts General Hospital
name: Paul E. Goss, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
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 Breast Cancer. 2007 Dec;7(11):895-900. doi: 10.3816/CBC.2007.n.057. No abstract available.
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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.