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

RATIONALE: Hormone therapy using exemestane may fight breast cancer by reducing the production of estrogen and progesterone.

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works in preventing cancer in postmenopausal women who are at increased risk of developing breast cancer.

Study Type: Interventional

Study Design: Prevention, Randomized, Double-Blind, Placebo Control

Study Primary Completion Date: June 2010

OBJECTIVES:

Primary - Compare the incidence of invasive breast cancer in postmenopausal women at increased risk of developing breast cancer when treated with exemestane vs placebo.

Secondary - Compare reduction in total incidence of invasive and non-invasive (ductal carcinoma in situ) breast cancer in patients treated with these regimens. - Compare reduction in total incidence of receptor-negative invasive breast cancer in patients treated with exemestane vs placebo. - Compare the incidence of lobular cancer in situ and atypical ductal hyperplasia in patients treated with these regimens. - Compare the number of clinical breast biopsies in patients treated with these regimens. - Compare the incidence of all clinical fractures, and specifically hip and vertebral fractures, in patients treated with these regimens. - Compare the incidence of clinically relevant cardiac events (i.e., significant coronary heart disease) in patients treated with these regimens. - Compare the impact of these regimens on menopausal symptoms and quality of life of these patients. - Compare adverse effects of these regimens in these patients. - Compare the incidence of other malignancies in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to concurrent low dose (≤ 100 mg/day) aspirin use (yes vs no) and Gail score (≤ 2 vs > 2). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral exemestane once daily for 5 years. - Arm II: Patients receive oral placebo once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 6 months for 1 year, and then annually for 4 years.

Patients are followed every 6 months for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,560 patients (2,280 per treatment arm) will be accrued for this study within 3 years.

Intervention(s) in this Clinical Trial

• Drug: exemestane
  • Given orally
• Other: placebo
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral exemestane once daily for 5 years.
• Placebo Comparator: Arm II
  • Patients receive oral placebo once daily for 5 years.

Primary Measures

• Invasive breast cancer-free survival after 38 events (about 4 years after start of study)
  • Safety Issue?: No

Secondary Measures

• Invasive and noninvasive breast cancer-free survival at about 4 years after start of study
  • Safety Issue?: No
• Clinical fracture rate at about 4 years after start of study
  • Safety Issue?: No
• Cardiac events at about 4 years after start of study
  • Safety Issue?: No
• Menopausal symptoms as assessed by MENQOL questionnaire at about 4 years after start of study
  • Safety Issue?: No
• Quality of Life assessed by SF36 at about 4 years after start of study
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• 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 or lobular carcinoma in situ on breast biopsy
• Prior ductal carcinoma in situ (DCIS) treated with mastectomy
• No prior DCIS treated with adjuvant tamoxifen
• No prior invasive breast cancer
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS:

• Age
• 35 and over
• Sex
• Female
• Menopausal status
• Postmenopausal, defined as one of the following:
• > 50 years of age with no spontaneous menses for at least 12 months before study entry
• ≤ 50 years of age 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
• Bilateral oophorectomy
• Performance status
• Not specified
• Life expectancy
• Not specified
• Hematopoietic
• Not specified
• Hepatic
• Not specified
• Renal
• Not specified
• Other
• 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
• Willing to complete quality of life questionnaires in either English or French

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• Not specified
• Chemotherapy
• Not specified
• Endocrine therapy
• See Disease Characteristics
• 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 concurrent endocrine therapy
• No concurrent estrogens, androgens, or progesterones
• Radiotherapy
• Not specified
• Surgery
• See Disease Characteristics
• See Menopausal status
• Other
• More than 30 days or 5 half-lives since prior investigational drugs
• 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

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 Sponsor: National Cancer Institute of Canada

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on July 02, 2009

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

Study ID Number: CDR0000363802

ClinicalTrials.gov Identifier: NCT00083174

Health Authority: Unspecified

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

Web site for additional information