Medroxyprogesterone in Treating Women With Breast Cancer

Condition(s) targeted: Breast Cancer; Endometrial Cancer

Intervention: medroxyprogesterone (Drug); tamoxifen citrate (Drug); adjuvant therapy (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Southwest Oncology Group

Official(s) and/or principal investigator(s):
Ronald K. Potkul, MD, Study Chair, Affiliation: Loyola University
Barbara L. Smith, MD, PhD, Study Chair, Affiliation: Massachusetts General Hospital

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.

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

Study design: Prevention, Randomized, Active Control

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

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

MBCCOP - Gulf Coast, Mobile, Alabama 36607, United States

Providence Alaska Medical Center, Anchorage, Alaska 99519-6604, United States

Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson, Arizona 85724, United States

CCOP - Western Regional, Arizona, Phoenix, Arizona 85006-2726, United States

Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix, Arizona 85012, United States

Veterans Affairs Medical Center - Tucson, Tucson, Arizona 85723, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Veterans Affairs Medical Center - Little Rock, Little Rock, Arkansas 72205, United States

CCOP - Bay Area Tumor Institute, Oakland, California 94609-3305, United States

CCOP - Santa Rosa Memorial Hospital, Santa Rosa, California 95403, United States

Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange, California 92868, United States

City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States

Naval Medical Center - San Diego, San Diego, California 92134-3202, United States

Rebecca and John Moores UCSD Cancer Center, La Jolla, California 92093-0658, United States

University of California Davis Cancer Center, Sacramento, California 95817, United States

USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California 90033, United States

Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda, California 92357, United States

Veterans Affairs Outpatient Clinic - Martinez, Martinez, California 94553, United States

University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora, Colorado 80010, United States

Veterans Affairs Medical Center - Denver, Denver, Colorado 80220, United States

CCOP - Christiana Care Health Services, Newark, Delaware 19713, United States

Lombardi Cancer Center at Georgetown University Medical Center, Washington, District of Columbia 20007, United States

MBCCOP - Howard University Cancer Center, Washington, District of Columbia 20060, United States

Broward General Medical Center, Fort Lauderdale, Florida 33316, United States

CCOP - Mount Sinai Medical Center, Miami Beach, Florida 33140, United States

Veterans Affairs Medical Center - Tampa (Haley), Tampa, Florida 33612, United States

CCOP - Atlanta Regional, Atlanta, Georgia 30342-1701, United States

MBCCOP - Hawaii, Honolulu, Hawaii 96813, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood, Illinois 60153-5500, United States

CCOP - Central Illinois, Decatur, Illinois 62526, United States

CCOP - Illinois Oncology Research Association, Peoria, Illinois 61615-7828, United States

Louis A. Weiss Memorial Hospital, Chicago, Illinois 60640, United States

MBCCOP - University of Illinois at Chicago, Chicago, Illinois 60612, United States

University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States

Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago, Illinois 60612, United States

Veterans Affairs Medical Center - Hines, Hines, Illinois 60141, United States

West Suburban Center for Cancer Care, River Forest, Illinois 60305, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7353, United States

Veterans Affairs Medical Center - Wichita, Wichita, Kansas 67218, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084, United States

Veterans Affairs Medical Center - Lexington, Lexington, Kentucky 40502-2236, United States

Louisiana State University Health Sciences Center - Shreveport, Shreveport, Louisiana 71130-3932, United States

MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States

Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans, Louisiana 70112, United States

Veterans Affairs Medical Center - New Orleans, New Orleans, Louisiana 70112, United States

Veterans Affairs Medical Center - Shreveport, Shreveport, Louisiana 71101-4295, United States

Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore, Maryland 21201, United States

Cancer Research Center at Boston Medical Center, Boston, Massachusetts 02118, United States

UMASS Memorial Cancer Center - University Campus, Worcester, Massachusetts 01655, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

CCOP - Beaumont, Royal Oak, Michigan 48073-6769, United States

CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States

CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan 48106, United States

Josephine Ford Cancer Center at Henry Ford Health System, Detroit, Michigan 48202, United States

Providence Cancer Institute at Providence Hospital - Southfield, Southfield, Michigan 48075, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0948, United States

Veterans Affairs Medical Center - Detroit, Detroit, Michigan 48201-1932, United States

University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Veterans Affairs Medical Center - Jackson, Jackson, Mississippi 39216, United States

CCOP - Cancer Research for the Ozarks, Springfield, Missouri 65807, United States

CCOP - Kansas City, Kansas City, Missouri 64131, United States

CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States

Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis, Missouri 63110, United States

St. Louis University Hospital Cancer Center, Saint Louis, Missouri 63110, United States

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-7680, United States

New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett, New Hampshire 03106, United States

Cooper University Hospital, Camden, New Jersey 08103, United States

MBCCOP - University of New Mexico HSC, Albuquerque, New Mexico 87131, United States

Veterans Affairs Medical Center - Albuquerque, Albuquerque, New Mexico 87108-5138, United States

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse, New York 13057, United States

Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States

Mount Sinai Medical Center, New York, New York 10029, United States

North Shore University Hospital, Manhasset, New York 11030, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York 10016, United States

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States

CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States

FirstHealth Moore Regional Hospital, Pinehurst, North Carolina 28374, United States

Lenoir Memorial Hospital Cancer Center, Kinston, North Carolina 28503-1678, United States

NorthEast Oncology Associates - Concord, Concord, North Carolina 28025, United States

Veterans Affairs Medical Center - Asheville, Asheville, North Carolina 28805, United States

Arthur G. James Cancer Hospital at Ohio State University, Columbus, Ohio 43210-1240, United States

CCOP - Columbus, Columbus, Ohio 43206, United States

CCOP - Dayton, Dayton, Ohio 45429, United States

Charles M. Barrett Cancer Center at University Hospital, Cincinnati, Ohio 45267-0501, United States

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195-9001, United States

Veterans Affairs Medical Center - Cincinnati, Cincinnati, Ohio 45220-2288, United States

Veterans Affairs Medical Center - Dayton, Dayton, Ohio 45428-1002, United States

Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States

Cancer Institute at Oregon Health and Science University, Portland, Oregon 97201-3098, United States

CCOP - Columbia River Oncology Program, Portland, Oregon 97225, United States

Veterans Affairs Medical Center - Portland, Portland, Oregon 97207, United States

CCOP - Greenville, Greenville, South Carolina 29615, United States

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States

Veterans Affairs Medical Center - Charleston, Charleston, South Carolina 29401-5799, United States

University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis, Tennessee 38104, United States

Veterans Affairs Medical Center - Memphis, Memphis, Tennessee 38104, United States

Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200, United States

CCOP - Scott and White Hospital, Temple, Texas 76508, United States

Harrington Cancer Center, Amarillo, Texas 79106, United States

University of Texas - MD Anderson Cancer Center, Houston, Texas 77030-4095, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States

University of Texas Medical Branch, Galveston, Texas 77555-0565, United States

Veterans Affairs Medical Center - Amarillo, Amarillo, Texas 79106, United States

Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio, Texas 78229, United States

Veterans Affairs Medical Center - Temple, Temple, Texas 76504, United States

Huntsman Cancer Institute, Salt Lake City, Utah 84112-5550, United States

Veterans Affairs Medical Center - Salt Lake City, Salt Lake City, Utah 84148, United States

Vermont Cancer Center at University of Vermont, Burlington, Vermont 05401-3498, United States

MBCCOP - Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke, Virginia 24014, United States

Virginia Oncology Associates - Norfolk, Norfolk, Virginia 23502, United States

CCOP - Northwest, Tacoma, Washington 98405-0986, United States

CCOP - Virginia Mason Research Center, Seattle, Washington 98101, United States

Puget Sound Oncology Consortium, Seattle, Washington 98109, United States

Veterans Affairs Medical Center - Seattle, Seattle, Washington 98108, United States

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

Starting date: March 1997
Last updated: May 23, 2008