S9630, Medroxyprogesterone in Treating Women With Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00002920
First received: November 1, 1999
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Endometrial Cancer
Drug: medroxyprogesterone
Drug: tamoxifen citrate
Procedure: adjuvant therapy
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Endometrial pathologic diagnosis [ Time Frame: 2 years after registration ] [ Designated as safety issue: No ]
    Endometrial pathologic diagnosis at 2 years after registration


Secondary Outcome Measures:
  • Endometrial pathologic diagnosis [ Time Frame: 5 years after registration ] [ Designated as safety issue: No ]
    Endometrial pathologic diagnosis at 5 years after registration


Enrollment: 313
Study Start Date: March 1997
Study Completion Date: December 2009
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tamoxifen alone
Tamoxifen alone x 5 years
Drug: tamoxifen citrate Procedure: adjuvant therapy
Experimental: Tamoxifen plus MPA
Tamoxifen Plus Medroxyprogesterone Acetate (MPA) x 5 years
Drug: medroxyprogesterone Drug: tamoxifen citrate Procedure: adjuvant therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002920

  Show 122 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
Investigators
Study Chair: Ronald K. Potkul, MD Loyola University
Study Chair: Barbara L. Smith, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00002920     History of Changes
Other Study ID Numbers: CDR0000065314, CALGB-49901, S9630, U10CA037429, U10CA032102
Study First Received: November 1, 1999
Last Updated: October 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
endometrial cancer
stage I breast cancer
stage II breast cancer
ductal breast carcinoma in situ
lobular breast carcinoma in situ
Paget disease of the breast

Additional relevant MeSH terms:
Breast Neoplasms
Endometrial Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Medroxyprogesterone
Medroxyprogesterone Acetate
Tamoxifen
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on September 15, 2014