S9630, Medroxyprogesterone in Treating Women With Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002920
• Other study ID #: CDR0000065314
• Secondary ID: CALGB-49901S9630
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: October 30, 2012
• Start date: March 1997
• Est. completion date: December 2009

Study information

• Verified date: October 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: December 2009
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Endometrial Cancer

Intervention

Drug:
• medroxyprogesterone

• tamoxifen citrate

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Harrington Cancer Center	Amarillo	Texas
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital at Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	NorthEast Oncology Associates - Concord	Concord	North Carolina
United States	CCOP - Dayton	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Loma Linda (Pettis)	Loma Linda	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Cancer Institute at Methodist Central Hospital	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)	Phoenix	Arizona
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	University of California Davis Cancer Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	St. Louis University Hospital Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Naval Medical Center - San Diego	San Diego	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Cancer Institute at Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	CCOP - Northwest	Tacoma	Washington
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Southwest Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endometrial pathologic diagnosis	Endometrial pathologic diagnosis at 2 years after registration	2 years after registration	No
Secondary	Endometrial pathologic diagnosis	Endometrial pathologic diagnosis at 5 years after registration	5 years after registration	No