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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Grupo Espanol de Investigacion del Cancer de Mama
UNICANCER
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00083174
First received: May 14, 2004
Last updated: February 7, 2014
Last verified: February 2014
Results First Received: November 7, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Breast Cancer
Intervention: Drug: exemestane

  Participant Flow
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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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Participant Flow:   Overall Study
    Exemestane     Placebo  
STARTED     2285     2275  
COMPLETED     2285 [1]   2275 [1]
NOT COMPLETED     0     0  
[1] All women randomized were included in the analysis based on intent-to-treat principle.



  Baseline Characteristics
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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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am
Total Total of all reporting groups

Baseline Measures
    Exemestane     Placebo     Total  
Number of Participants  
[units: participants]
  2285     2275     4560  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     1458     1481     2939  
>=65 years     827     794     1621  
Age  
[units: years]
Mean ± Standard Deviation
  63.1  ± 7.2     63.1  ± 7.0     63.1  ± 7.1  
Gender  
[units: participants]
     
Female     2285     2275     4560  
Male     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
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1.  Primary:   Invasive Breast Cancer Incidence (Breast Cancer-Free Survival)   [ Time Frame: Over 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 study (median follow-up 35 months)  
Safety Issue No  

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
Exemestane 25 mg of exemestane tablet daily
Placebo Placebo tablet daily

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  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
Method [2] Log Rank
P Value [3] 0.002
Hazard Ratio (HR) [4] 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] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Total Incidence of Invasive and Non-invasive (DCIS) Breast Cancer   [ Time Frame: Over 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 study (median follow-up 35 months)  
Safety Issue No  

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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  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
Method [2] Log Rank
P Value [3] 0.004
Hazard Ratio (HR) [4] 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] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Incidence of Lobular Carcinoma in Situ, Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia Events   [ Time Frame: Over 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 study (median follow-up 35 months)  
Safety Issue No  

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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  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
Method [2] Log Rank
P Value [3] 0.07
Hazard Ratio (HR) [4] 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] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] 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.
[4] Other relevant estimation information:
  No text entered.



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

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

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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  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



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

Measure Type Secondary
Measure Title Incidence of All Clinical Fractures
Measure Description No text entered.
Time Frame During protocol treatment (up to 5 years)  
Safety Issue Yes  

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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  2240     2248  
Incidence of All Clinical Fractures  
[units: participants]
  149     143  

No statistical analysis provided for Incidence of All Clinical Fractures



6.  Secondary:   Incidence of Clinically Relevant Cardiac Events   [ Time Frame: During protocol treatment (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 (up to 5 years)  
Safety Issue Yes  

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

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

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  2240     2248  
Incidence of Clinically Relevant Cardiac Events  
[units: participants]
  106     111  

No statistical analysis provided for Incidence of Clinically Relevant Cardiac Events



7.  Secondary:   Incidences of Other Malignancies   [ Time Frame: Over 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 study (median follow-up 35 months)  
Safety Issue Yes  

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
Exemestane one 25 mg tablet daily in am
Placebo one tablet daily in am

Measured Values
    Exemestane     Placebo  
Number of Participants Analyzed  
[units: participants]
  2240     2248  
Incidences of Other Malignancies  
[units: participants]
  50     42  

No statistical analysis provided for Incidences of Other Malignancies



8.  Primary:   Frequency of Serious Adverse Events   [ Time Frame: 5 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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