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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between February 11, 2004, and March 23, 2010, 4560 women were recruited in medical clinics.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligibility of women was first checked before the randomization to the trial.

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am
Open-label Extension: Exemestane one 25 mg tablet daily in am

Participant Flow for 2 periods

Period 1:   Randomization Period
    Randomization Period: Exemestane   Randomization Period: Placebo   Open-label Extension: Exemestane
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 2:   Open-label Extension
    Randomization Period: Exemestane   Randomization Period: Placebo   Open-label Extension: Exemestane
STARTED   0   0   2831 
COMPLETED   0   0   2831 
NOT COMPLETED   0   0   0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am
Total Total of all reporting groups

Baseline Measures
   Randomization Period: Exemestane   Randomization Period: Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 2285   2275   4560 
Age 
[Units: Participants]
Count of 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 
[Units: Years]
Mean (Standard Deviation)
 63.1  (7.2)   63.1  (7.0)   63.1  (7.1) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      2285 100.0%      2275 100.0%      4560 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 
Region of Enrollment 
[Units: Participants]
     
United States   1416   1408   2824 
France   9   10   19 
Canada   643   642   1285 
Spain   217   215   432 


  Outcome Measures

1.  Primary:   Percentage of Women With Serious Adverse Events   [ Time Frame: 5 years open-label extension period ]

Measure Type Primary
Measure Title Percentage of Women With Serious Adverse Events
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Open-label Extension: Exemestane

one 25 mg tablet daily in am

exemestane: one 25 mg tablet daily in am


Measured Values
   Open-label Extension: Exemestane 
Participants Analyzed   2831 
Percentage of Women With Serious Adverse Events 
[Units: Percentage of women]
Number (95% Confidence Interval)
 0.0 
 (0.0 to 0.5) 

No statistical analysis provided for Percentage of Women With Serious Adverse Events



2.  Primary:   Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)   [ Time Frame: Over randomization period of study (median follow-up 35 months) ]

Measure Type Primary
Measure Title Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)
Measure 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)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
intention to treat (ITT)

Reporting Groups
  Description
Randomization Period: Exemestane 25 mg of exemestane tablet daily
Randomization Period: Placebo Placebo tablet daily

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2285   2275 
Invasive Breast Cancer Incidence (Breast Cancer-Free Survival) 
[Units: Percentage of cases/follow-up person-yr]
Number (95% Confidence Interval)
 0.19 
 (0.08 to 0.30) 
 0.55 
 (0.36 to 0.73) 


Statistical Analysis 1 for Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.002
Hazard Ratio (HR) [5] 0.35
95% Confidence Interval 0.18 to 0.70
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



3.  Secondary:   Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer   [ Time Frame: Over randomization period of study (median follow-up 35 months) ]

Measure Type Secondary
Measure Title Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer
Measure 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)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT)

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2285   2275 
Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer 
[Units: Percentage of cases/follow-up person-yr]
Number (95% Confidence Interval)
 0.35 
 (0.20 to 0.50) 
 0.77 
 (0.54 to 0.99) 


Statistical Analysis 1 for Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.004
Hazard Ratio (HR) [5] 0.47
95% Confidence Interval 0.27 to 0.79
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



4.  Secondary:   Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events   [ Time Frame: Over randomization period of study (median follow-up 35 months) ]

Measure Type Secondary
Measure Title Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events
Measure Description No text entered.
Time Frame Over randomization period of study (median follow-up 35 months)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT)

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2285   2275 
Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events 
[Units: Percentage of cases/follow-up person-yr]
Number (95% Confidence Interval)
 0.07 
 (0.00 to 0.15) 
 0.20 
 (0.08 to 0.32) 


Statistical Analysis 1 for Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] 0.07
Hazard Ratio (HR) [5] 0.36
95% Confidence Interval 0.11 to 1.12
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   Number of Clinical Breast Biopsies   [ Time Frame: Over randomization period of study (median follow-up 35 months) ]

Measure Type Secondary
Measure Title Number of Clinical Breast Biopsies
Measure Description No text entered.
Time Frame Over randomization period of study (median follow-up 35 months)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Women who had at least one clinical breast biopsy

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   81   118 
Number of Clinical Breast Biopsies 
[Units: Number of clinical breast biopsies]
Median (Full Range)
 1 
 (1 to 3) 
 1 
 (1 to 3) 

No statistical analysis provided for Number of Clinical Breast Biopsies



6.  Secondary:   Incidence of All Clinical Fractures   [ Time Frame: During protocol treatment over randomization period of study (up to 5 years) ]

Measure Type Secondary
Measure Title Incidence of All Clinical Fractures
Measure Description No text entered.
Time Frame During protocol treatment over randomization period of study (up to 5 years)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Women who have received treatment

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2240   2248 
Incidence of All Clinical Fractures 
[Units: Participants]
 149   143 

No statistical analysis provided for Incidence of All Clinical Fractures



7.  Secondary:   Incidence of Clinically Relevant Cardiac Events   [ Time Frame: During protocol treatment in randomization period (up to 5 years) ]

Measure Type Secondary
Measure Title Incidence of Clinically Relevant Cardiac Events
Measure 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)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Women who received treatment during randomization period

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2240   2248 
Incidence of Clinically Relevant Cardiac Events 
[Units: Participants]
 106   111 

No statistical analysis provided for Incidence of Clinically Relevant Cardiac Events



8.  Secondary:   Incidences of Other Malignancies   [ Time Frame: Over randomization period of study (median follow-up 35 months) ]

Measure Type Secondary
Measure Title Incidences of Other Malignancies
Measure Description Other malignancies includes any other malignancy which is not in breast.
Time Frame Over randomization period of study (median follow-up 35 months)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Women who have received treatment

Reporting Groups
  Description
Randomization Period: Exemestane one 25 mg tablet daily in am
Randomization Period: Placebo one tablet daily in am

Measured Values
   Randomization Period: Exemestane   Randomization Period: Placebo 
Participants Analyzed   2240   2248 
Incidences of Other Malignancies 
[Units: Participants]
 50   42 

No statistical analysis provided for Incidences of Other Malignancies




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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
e-mail: pgoss@partners.org


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.

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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