Official Title: “A RANDOMIZED COMPARISON OF MEDROXYPROGESTERONE ACETATE (MA) AND OBSERVATION FOR PREVENTION OF ENDOMETRIAL PATHOLOGY IN POSTMENOPAUSAL BREAST CANCER PATIENTS TREATED WITH TAMOXIFEN, PHASE III”

RATIONALE: It is not yet known whether medroxyprogesterone is effective in preventing endometrial disorder in patients with breast cancer who are taking tamoxifen.

PURPOSE: Randomized phase III trial to study the effectiveness of medroxyprogesterone in preventing endometrial disorder in postmenopausal women who have ductal carcinoma in situ, lobular carcinoma in situ, Paget's disease of the nipple, stage I breast cancer, or stage II breast cancer and who are taking tamoxifen.

Study Type: Interventional

Study Design: Prevention, Randomized, Active Control

OBJECTIVES: - Compare endometrial pathologic diagnoses (proliferative changes, simple or cystic hyperplasia, complex adenomatous hyperplasia, hyperplasia with atypia, and carcinoma) in postmenopausal women with breast carcinoma treated with adjuvant tamoxifen who are randomly assigned to medroxyprogesterone acetate (MA) vs observation. - Compare endometrial pathologic diagnoses (persistent endometrial hyperplasia, atypia, or carcinoma) resulting in tamoxifen discontinuation and intermittent bleeding in patients treated with these regimens. - Characterize the incidence of spontaneous regression and progression of simple or cystic hyperplasia in these patients. - Characterize endometrial biopsy results using different endometrial stripe width cut-off points, for cases in which the width is at least 5 mm by endovaginal ultrasound in patients receiving tamoxifen. - Compare changes over time in endometrial oncogene expression (e.g., c-fos, c-jun, p53, IGF1) and receptor status in patients receiving tamoxifen with or without prior chemotherapy who are randomly assigned to MA vs observation. - Describe the associations among change in gene expression, receptor status, endometrial abnormality, length of tamoxifen exposure, and prior chemotherapy in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to adjuvant chemotherapy (yes vs no), number of positive nodes (0-3 vs at least 4), and endovaginal sonogram endometrial stripe (less than 5 mm vs at least 5 mm). Patients are randomized to 1 of 2 arms.

All patients receive adjuvant oral tamoxifen daily for five years. - Arm I: Patients undergo observation. - Arm II: Patients receive oral medroxyprogesterone acetate on days 1-14. Treatment repeats every 3 months for 5 years.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 330 patients (165 per arm) will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: medroxyprogesterone
• Drug: tamoxifen citrate
• Procedure: adjuvant therapy

DISEASE CHARACTERISTICS:

• One of the following histologically proven diagnoses:
• Primary invasive adenocarcinoma of the unilateral or bilateral breast
• Stage I, IIA, or IIB (T1-3, N0-1, M0)
• No recurrent invasive breast cancer
• Ductal carcinoma in situ (DCIS)
• Lobular carcinoma in situ (LCIS) with microinvasion
• Paget's disease of the nipple
• No sarcoma, lymphoma, or apocrine, adenocystic, or squamous cell cancer of the breast
• Currently free of breast cancer (no evidence of disease)
• No evidence of distant disease on chest x-ray or chest CT scan and mammogram of the opposite breast within the past year
• Prior definitive local treatment of primary lesion (mastectomy or breast-sparing procedure with radiotherapy) and either axillary node or sentinel node biopsy
• Surgical margins clear of both infiltrating carcinoma (any type) and DCIS
• No gross or microscopically positive margins except:
• Invasive cancer or DCIS at the focal margin treated with definitive radiotherapy
• Gross or LCIS at the final margin
• Biopsy requirement waived for DCIS or LCIS with minimal microinvasion
• Patients with breast-sparing procedure must have received or be planning to receive radiotherapy at start of tamoxifen treatment
• No endometrial simple or cystic hyperplasia, proliferative changes, complex (adenomatous) or atypical hyperplasia, or carcinoma
• Patients must be planning one of the following:
• Starting adjuvant tamoxifen for five years OR
• Started tamoxifen within 28 days prior to study and planning to receive adjuvant tamoxifen for five years
• Hormone receptor status:
• Candidate for adjuvant tamoxifen therapy

PATIENT CHARACTERISTICS:

Age:

• Adult

Sex:

• Female

Menopausal status:

• Postmenopausal defined as:
• At least 1 year since last menstrual period
• At least 2 months since bilateral oophorectomy prior to breast cancer diagnosis
• 4-12 months since last menstrual period and FSH elevated to postmenopausal range
• Postmenopausal estrogen therapy and 55 years of age or older

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Fertile patients must use effective contraception during and for at least 2 months after study
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer currently in complete remission
• No concurrent nonmalignant-related illness that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Adjuvant chemotherapy allowed
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• No prior hormonal treatment for breast cancer (except tamoxifen)
• No concurrent postmenopausal estrogen therapy

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics
• No prior or concurrent hysterectomy

Other:

• No prior or current participation in an adjuvant intergroup trial

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Southwest Oncology Group

Overall Clinical Trial Officials and Contacts

Ronald K. Potkul, MD Study Chair Loyola University  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002920

Study ID Number: CDR0000065314

ClinicalTrials.gov Identifier: NCT00002920

Health Authority: United States: Federal Government

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