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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: exemestane


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Exemestane<br>one 25 mg tablet daily in am | Drug: exemestane<br>* one 25 mg tablet daily in am<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer