Exemestane in Treating Postmenopausal Women With Resected Stage I, Stage II, or Stage IIIA Breast Cancer Who Have Completed 5 Years of Tamoxifen

Study Overview
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Brief Summary
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by reducing the production of estrogen by the tumor cells. It is not yet known whether exemestane is effective in preventing the recurrence of breast cancer. PURPOSE: Randomized phase III trial to study the effectiveness of exemestane in preventing cancer recurrence in postmenopausal women who have resected stage I, stage II, or stage IIIA breast cancer and have completed 5 years of tamoxifen.

Detailed Description
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OBJECTIVES: Determine whether the administration of 5 years of exemestane after 5 years of tamoxifen therapy is more effective than 5 years of prior tamoxifen therapy alone in prolonging disease-free survival, overall survival, and time to treatment failure in postmenopausal women with resected stage I, II, or IIIA breast cancer. Determine the effect of tamoxifen withdrawal on bone, in terms of height, fractures, and total alkaline phosphatase in these patients and on bone mineral density and bone biochemical markers in a subset of patients. Determine the effect of exemestane on bone loss after tamoxifen withdrawal in these patients. Evaluate the quality of life of a subset of these patients. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral exemestane daily for 5 years. Arm II (closed as of 10/15/03): Patients receive an oral placebo daily for 5 years. Quality of life is assessed at baseline and then every 6 months for 5.5 years. Patients are followed every 6 months for 6 years and then annually thereafter. PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 3 years and 4 months.

Official Title
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A Randomized Trial Evaluating The Effect Of Exemestane In Clinical Stage T1-3 N0-1 M0 Postmenopausal Breast Cancer Patients Completing At Least Five Years Of Tamoxifen Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: exemestane
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive adenocarcinoma of the breast at time of original diagnosis Tumor confined to the breast and ipsilateral axilla on clinical exam (T1-3, N0-1, M0) (stage I-IIIA) No ipsilateral lymph nodes clinically fixed to one another or to other structures (N2 disease) at time of original diagnosis Prior surgical resection, including 1 of the following: Total mastectomy and axillary dissection (modified radical mastectomy) OR Lumpectomy and axillary dissection Prior post-lumpectomy breast radiotherapy required Prior sentinel node biopsy allowed with the exception of the following: If any sentinel node is histologically positive by hematoxylin and eosin (H & E) OR histologically suspicious on H & E and confirmed positive by immunohistochemistry then the patient must have a complete axillary dissection Previously resected margins must be clear of invasive tumor and ductal carcinoma in situ Currently disease free Previously treated with tamoxifen for 57-66 months Completed tamoxifen within the past 180 days No bilateral malignancy or mass in the opposite breast suspicious for malignancy unless biopsy proven negative No local, regional, or distant recurrence of disease or second primary breast malignancy (including contralateral breast cancer) No advanced disease at time of original diagnosis (e.g., ulceration, erythema, infiltration of the skin or underlying chest wall [complete fixation], peau d'orange, or skin edema of any magnitude) Tethering or dimpling of the skin or nipple inversion allowed Current skeletal pain allowed if a bone scan and/or radiologic exam is negative for metastatic disease Hormone receptor status: Primary tumor estrogen receptor (ER) positive AND/OR Progesterone receptor positive Borderline ER positive tumors allowed if previously treated with tamoxifen PATIENT CHARACTERISTICS: Age: Postmenopausal Sex: Female Menopausal status: Postmenopausal, defined as 1 of the following: Prior bilateral oophorectomy Absence of spontaneous menstrual cycle for more than 1 year Follicle-stimulating hormone within the postmenopausal range if under 55 and had a prior hysterectomy without a bilateral oophorectomy Performance status: Not specified Life expectancy: At least 10 years Hematopoietic: Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin normal Hepatic: Bilirubin less than 2 times upper limit of normal (ULN) SGOT or SGPT no greater than 2.5 times ULN Alkaline phosphatase less than 2 times ULN No systemic hepatic disease that would preclude study participation Renal: Creatinine no greater than 1.5 times ULN No systemic renal disease that would preclude study participation Cardiovascular: No systemic cardiovascular disease that would preclude study participation Other: No other malignancy within the past 5 years except effectively treated squamous cell or basal cell skin cancer, surgically treated carcinoma in situ of the cervix, or surgically treated lobular carcinoma in situ of the ipsilateral or contralateral breast No nonmalignant systemic disease that would preclude study participation No psychiatric or addictive disorder that would preclude informed consent Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior adjuvant chemotherapy allowed if administered concurrently with or prior to tamoxifen Endocrine therapy: See Disease Characteristics No concurrent estrogen, progesterone, clomiphene, testosterone, gonadotropin-releasing hormone, oral contraceptives, selective estrogen-receptor modulators, or dehydroepiandrosterone (DHEA) Estring or estrogen vaginal cream at 0.3 mg or 1/8 of an applicator applied vaginally 3 times a week allowed No other concurrent systemic hormonal therapy (e.g., tamoxifen or raloxifene) Radiotherapy: See Disease Characteristics Prior post-mastectomy loco-regional radiotherapy or post-lumpectomy regional radiotherapy allowed Surgery: See Disease Characteristics Other: Prior participation in other adjuvant NSABP study allowed if study was reported in peer-review publication or tamoxifen was not a study drug Concurrent bisphosphonates or calcitonin for prevention or treatment of osteoporosis allowed Concurrent statins (simvastatin, pravastatin, fluvastatin, atorvastatin, or lovastatin) or other drugs to control lipid levels allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Exemestane | Drug: exemestane<br>* 25 mg for 5 years<br>|
| Placebo Comparator: Group 2<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | Every 12 months until breast cancer recurrence, second primary cancer or death from any cause. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Death from any cause | 
| Time to treatment failure |  | time from randomization to recurrence or contralateral second primary cancer | 
| Bone measure as measured by total alkaline phosphatase, fracture history, and height measurement |  | measurements taken at regular intervals from randomization through 6 years following randomiztion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer, stage II breast cancer, stage IIIA breast cancer