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”

RATIONALE: The MAP.3 study was designed to tests whether hormone therapy using exemestane may prevent breast cancer by reducing the production of estrogen and progesterone. This study was analyzed in April 2011 and showed a 65% reduction in the incidence of invasive breast cancer in women receiving exemestane.

PURPOSE: The study protocol was amended in May 2011 and the purpose of the study is now to allow all study participants to have the opportunity to complete 5 years of exemestane.

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 was a randomized, double-blind, placebo-controlled, multicentre study.

Following the amendment of May 2011, the study is now open-label and all eligible patients are receiving exemestane 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. Of these, up to 2800 women may participate in the amended study.

Intervention(s) in this Clinical Trial

• Drug: exemestane
  • one 25 mg tablet daily in am

Arms, Groups and Cohorts in this Clinical Trial

• Other: Exemestane
  • one 25 mg tablet daily in am

Primary Measures

• Frequency of serious adverse events
  • Time Frame: 5 years
    Safety Issue?: Yes

DISEASE CHARACTERISTICS:

Previous:

• 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
• Hormone receptor status:
• Not specified

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:

• See Disease Characteristics
• See Menopausal status
• 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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: NCIC Clinical Trials Group Other

Overall Clinical Trial Officials and Contacts

Paul E. Goss, MD, PhD Study Chair Massachusetts General Hospital  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00083174

Study ID Number: MAP3

ClinicalTrials.gov Identifier: NCT00083174

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information