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

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ClinicalTrials.gov Identifier: NCT00083174
Recruitment Status : Completed
First Posted : May 17, 2004
Results First Posted : May 20, 2013
Last Update Posted : April 25, 2018
Sponsor:
Collaborators:
Grupo Espanol de Investigacion del Cancer de Mama
UNICANCER
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Breast Cancer
Intervention Drug: exemestane
Enrollment 4560
Recruitment Details Between February 11, 2004, and March 23, 2010, 4560 women were recruited in medical clinics.
Pre-assignment Details Eligibility of women was first checked before the randomization to the trial.
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo Open-label Extension: Exemestane
Hide Arm/Group Description one 25 mg tablet daily in am one tablet daily in am one 25 mg tablet daily in am
Period Title: Randomization Period
Started 2285 2275 0
Completed 2285 [1] 2275 [1] 0
Not Completed 0 0 0
[1]
All women randomized were included in the analysis based on intent-to-treat principle.
Period Title: Open-label Extension
Started 0 0 2831
Completed 0 0 2831
Not Completed 0 0 0
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo Total
Hide Arm/Group Description one 25 mg tablet daily in am one tablet daily in am Total of all reporting groups
Overall Number of Baseline Participants 2285 2275 4560
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2285 participants 2275 participants 4560 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1458
  63.8%
1481
  65.1%
2939
  64.5%
>=65 years
827
  36.2%
794
  34.9%
1621
  35.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2285 participants 2275 participants 4560 participants
63.1  (7.2) 63.1  (7.0) 63.1  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2285 participants 2275 participants 4560 participants
Female
2285
 100.0%
2275
 100.0%
4560
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2285 participants 2275 participants 4560 participants
United States 1416 1408 2824
France 9 10 19
Canada 643 642 1285
Spain 217 215 432
1.Primary Outcome
Title Percentage of Women With Serious Adverse Events
Hide Description Percentage of serious adverse events for women who choose to receive 5 years of exemestane as preventative therapy.
Time Frame 5 years open-label extension period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Postmenopausal women who were randomized to exemestane in original MAP.3 study and chose to continue to receive exemestane for up to 5 years and those randomized to placebo and decided to start 5 years of exemestane.
Arm/Group Title Open-label Extension: Exemestane
Hide Arm/Group Description:

one 25 mg tablet daily in am

exemestane: one 25 mg tablet daily in am

Overall Number of Participants Analyzed 2831
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of women
0.0
(0.0 to 0.5)
2.Primary Outcome
Title Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)
Hide Description 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.
Time Frame Over randomization period of study (median follow-up 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
intention to treat (ITT)
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
25 mg of exemestane tablet daily
Placebo tablet daily
Overall Number of Participants Analyzed 2285 2275
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of cases/follow-up person-yr
0.19
(0.08 to 0.30)
0.55
(0.36 to 0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomization Period: Exemestane, Randomization Period: Placebo
Comments The null hypothesis was no difference between two groups. The sample size estimate was based on an assumption of annual invasive breast cancer rate of 0.60% in the placebo group and 0.21% in exemestane group, a relative reduction of 65% with exemestane. To detect this with a two-sided 5% level and 90% power, a total of 38 cases of invasive breast cancer were required, projected to occur when 4560 women were randomly assigned in a 3-year period and then followed for an additional 1.2 years.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.18 to 0.70
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer
Hide Description 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.
Time Frame Over randomization period of study (median follow-up 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT)
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 2285 2275
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of cases/follow-up person-yr
0.35
(0.20 to 0.50)
0.77
(0.54 to 0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomization Period: Exemestane, Randomization Period: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.27 to 0.79
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events
Hide Description [Not Specified]
Time Frame Over randomization period of study (median follow-up 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT)
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 2285 2275
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of cases/follow-up person-yr
0.07
(0.00 to 0.15)
0.20
(0.08 to 0.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomization Period: Exemestane, Randomization Period: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.11 to 1.12
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Clinical Breast Biopsies
Hide Description [Not Specified]
Time Frame Over randomization period of study (median follow-up 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Women who had at least one clinical breast biopsy
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 81 118
Median (Full Range)
Unit of Measure: number of clinical breast biopsies
1
(1 to 3)
1
(1 to 3)
6.Secondary Outcome
Title Incidence of All Clinical Fractures
Hide Description [Not Specified]
Time Frame During protocol treatment over randomization period of study (up to 5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Women who have received treatment
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 2240 2248
Measure Type: Number
Unit of Measure: participants
149 143
7.Secondary Outcome
Title Incidence of Clinically Relevant Cardiac Events
Hide Description Events including myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes and all vascular deaths
Time Frame During protocol treatment in randomization period (up to 5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Women who received treatment during randomization period
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 2240 2248
Measure Type: Number
Unit of Measure: participants
106 111
8.Secondary Outcome
Title Incidences of Other Malignancies
Hide Description Other malignancies includes any other malignancy which is not in breast.
Time Frame Over randomization period of study (median follow-up 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Women who have received treatment
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo
Hide Arm/Group Description:
one 25 mg tablet daily in am
one tablet daily in am
Overall Number of Participants Analyzed 2240 2248
Measure Type: Number
Unit of Measure: participants
50 42
Time Frame Participants were followed for a median of 35 months over randomization period of study for randomization period and 5 years for open-label extension period
Adverse Event Reporting Description During 5 year open-label extension, only SAE was monitored.
 
Arm/Group Title Randomization Period: Exemestane Randomization Period: Placebo Open-label Extension: Exemestane
Hide Arm/Group Description one 25 mg tablet daily in am one tablet daily in am one 25 mg tablet daily in am
All-Cause Mortality
Randomization Period: Exemestane Randomization Period: Placebo Open-label Extension: Exemestane
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Randomization Period: Exemestane Randomization Period: Placebo Open-label Extension: Exemestane
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/2240 (1.74%)   26/2248 (1.16%)   0/2831 (0.00%) 
Cardiac disorders       
Supraven.arrhyth. Atrial fibrillation  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Cardiac ischemia/infarction  1  2/2240 (0.09%)  3/2248 (0.13%)  0/2831 (0.00%) 
Valvular heart disease  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Cardiac General - Other  1  2/2240 (0.09%)  1/2248 (0.04%)  0/2831 (0.00%) 
Endocrine disorders       
Endocrine - Other  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Eye disorders       
Ocular - Other  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Gastrointestinal disorders       
Colitis  1  2/2240 (0.09%)  1/2248 (0.04%)  0/2831 (0.00%) 
Diarrhea  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
Dysphagia  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Gastritis  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Incontinence, anal  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Nausea  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Obstruction, GI Stomach  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Vomiting  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
GI - Other  1  3/2240 (0.13%)  1/2248 (0.04%)  0/2831 (0.00%) 
General disorders       
Sudden death  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Pain Abdomen NOS  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Pain Back  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Pain Joint  1  2/2240 (0.09%)  0/2248 (0.00%)  0/2831 (0.00%) 
Syndromes - Other  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Pancreatitis  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Immune system disorders       
Allergic reaction  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Infections and infestations       
Infec.w.norm.ANC Upper airway NOS  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Infection (doc.clin.) Lung  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Infection - Other  1  2/2240 (0.09%)  1/2248 (0.04%)  0/2831 (0.00%) 
Metabolism and nutrition disorders       
ALT  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
AST  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
Alkaline phosphatase  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Creatinine  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
GGT  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Hypercalcemia  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthritis  1  2/2240 (0.09%)  3/2248 (0.13%)  0/2831 (0.00%) 
Fracture  1  2/2240 (0.09%)  1/2248 (0.04%)  0/2831 (0.00%) 
Musculoskeletal - Other  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Secondary Malignancy  1  2/2240 (0.09%)  0/2248 (0.00%)  0/2831 (0.00%) 
Nervous system disorders       
CNS ischemia  1  7/2240 (0.31%)  4/2248 (0.18%)  0/2831 (0.00%) 
Memory impairment  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Neuropathy-sensory  1  1/2240 (0.04%)  0/2248 (0.00%)  0/2831 (0.00%) 
Neurology - Other  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Renal and urinary disorders       
Renal failure  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnea  1  1/2240 (0.04%)  1/2248 (0.04%)  0/2831 (0.00%) 
Pulmonary - Other  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Urinary retention  1  0/2240 (0.00%)  1/2248 (0.04%)  0/2831 (0.00%) 
Vascular disorders       
Thrombosis/thrombus/embolism  1  0/2240 (0.00%)  2/2248 (0.09%)  0/2831 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE, version 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Randomization Period: Exemestane Randomization Period: Placebo Open-label Extension: Exemestane
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1963/2240 (87.63%)   1901/2248 (84.56%)   0/0 
Cardiac disorders       
hypertension  1  341/2240 (15.22%)  354/2248 (15.75%)  0/0 
Endocrine disorders       
hot flashes  1  900/2240 (40.18%)  718/2248 (31.94%)  0/0 
fatigue  1  525/2240 (23.44%)  465/2248 (20.69%)  0/0 
sweating  1  486/2240 (21.70%)  433/2248 (19.26%)  0/0 
insomnia  1  230/2240 (10.27%)  189/2248 (8.41%)  0/0 
Gastrointestinal disorders       
Diarrhea  1  118/2240 (5.27%)  75/2248 (3.34%)  0/0 
heartburn  1  332/2240 (14.82%)  289/2248 (12.86%)  0/0 
Nausea  1  155/2240 (6.92%)  122/2248 (5.43%)  0/0 
General disorders       
Pain Back  1  306/2240 (13.66%)  222/2248 (9.88%)  0/0 
pain extremity  1  153/2240 (6.83%)  122/2248 (5.43%)  0/0 
Pain Joint  1  665/2240 (29.69%)  606/2248 (26.96%)  0/0 
pain muscle  1  147/2240 (6.56%)  192/2248 (8.54%)  0/0 
Musculoskeletal and connective tissue disorders       
Arthritis  1  247/2240 (11.03%)  196/2248 (8.72%)  0/0 
Nervous system disorders       
dizziness  1  189/2240 (8.44%)  209/2248 (9.30%)  0/0 
mood alteration or depression  1  236/2240 (10.54%)  235/2248 (10.45%)  0/0 
Reproductive system and breast disorders       
vaginal dryness  1  352/2240 (15.71%)  343/2248 (15.26%)  0/0 
Respiratory, thoracic and mediastinal disorders       
cough  1  234/2240 (10.45%)  266/2248 (11.83%)  0/0 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE, version 3.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Paul Goss
Organization: Massachusetts General Hospital
Phone: 617-724-3118
Publications of Results:
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.
Responsible Party: Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
ClinicalTrials.gov Identifier: NCT00083174     History of Changes
Obsolete Identifiers: NCT00304486
Other Study ID Numbers: MAP3
CAN-NCIC-MAP3 ( Registry Identifier: PDQ )
PFIZER-EXEAPO-0028-150
ExCel
CDR0000363802 ( Other Identifier: PDQ )
First Submitted: May 14, 2004
First Posted: May 17, 2004
Results First Submitted: November 7, 2012
Results First Posted: May 20, 2013
Last Update Posted: April 25, 2018