S9630, Medroxyprogesterone in Treating Women With Breast Cancer

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 Overview

• Status: Completed
• Conditions: Breast Cancer; Endometrial Cancer
• Intervention / Treatment: Procedure: adjuvant therapy; Drug: tamoxifen citrate; Drug: medroxyprogesterone

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.

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • MBCCOP - Gulf Coast
  • Alaska
    • Anchorage, Alaska, United States, 99519-6604
      • Providence Alaska Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Western Regional, Arizona
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Loma Linda, California, United States, 92357
      • Veterans Affairs Medical Center - Loma Linda (Pettis)
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Diego, California, United States, 92134-3202
      • Naval Medical Center - San Diego
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20060
      • MBCCOP - Howard University Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • MBCCOP - University of Illinois at Chicago
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Maywood, Illinois, United States, 60153-5500
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Peoria, Illinois, United States, 61615-7828
      • CCOP - Illinois Oncology Research Association
    • River Forest, Illinois, United States, 60305
      • West Suburban Center for Cancer Care
  • Kansas
    • Kansas City, Kansas, United States, 66160-7353
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48109-0948
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University Hospital Cancer Center
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
  • New Hampshire
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology-Hematology, PA - Hooksett
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • East Syracuse, New York, United States, 13057
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10016
      • NYU School of Medicine's Kaplan Comprehensive Cancer Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Veterans Affairs Medical Center - Asheville
    • Concord, North Carolina, United States, 28025
      • NorthEast Oncology Associates - Concord
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
    • Kinston, North Carolina, United States, 28503-1678
      • Lenoir Memorial Hospital Cancer Center
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth Moore Regional Hospital
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital at Ohio State University
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45428-1002
      • Veterans Affairs Medical Center - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97207
      • Veterans Affairs Medical Center - Portland
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute at Methodist Central Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030-4095
      • University of Texas - MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center at University of Vermont
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Norfolk
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tamoxifen alone; Tamoxifen alone x 5 years	Procedure: adjuvant therapy; Drug: tamoxifen citrate
Experimental: Tamoxifen plus MPA; Tamoxifen Plus Medroxyprogesterone Acetate (MPA) x 5 years	Procedure: adjuvant therapy; Drug: tamoxifen citrate; Drug: medroxyprogesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial pathologic diagnosis	Endometrial pathologic diagnosis at 2 years after registration	2 years after registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial pathologic diagnosis	Endometrial pathologic diagnosis at 5 years after registration	5 years after registration

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI); Cancer and Leukemia Group B
• Investigators: Study Chair: Ronald K. Potkul, MD, Loyola University; Study Chair: Barbara L. Smith, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 1997
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 30, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: endometrial cancer; stage II breast cancer; stage I breast cancer; ductal breast carcinoma in situ; lobular breast carcinoma in situ; Paget disease of the breast
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Breast Diseases; Breast Neoplasms; Endometrial Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Contraceptive Agents, Male; Tamoxifen; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: CDR0000065314; U10CA032102 (U.S. NIH Grant/Contract); U10CA037429 (U.S. NIH Grant/Contract); CALGB-49901 (Other Identifier: CALGB); S9630 (Other Identifier: SWOG)