Hormone Replacement Therapy for Hot Flashes and/or Vaginal Symptoms in Postmenopausal Women Receiving Tamoxifen for Breast Cancer

A Phase III Prospective, Randomized, Double-Blind Clinical Trial of Hormone Replacement Therapy In Postmenopausal Women With A History Of Node-Negative Or Ductal Carcinoma In Situ Who Are Receiving Adjuvant Tamoxifen

RATIONALE: Hormone replacement therapy may be effective in managing the hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of hormone replacement therapy in managing hot flashes and/or vaginal symptoms in postmenopausal women who are receiving tamoxifen for breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Hot Flashes; Menopausal Symptoms
• Intervention / Treatment: Drug: medroxyprogesterone; Drug: conjugated estrogens

Detailed Description

OBJECTIVES:

• Determine the efficacy of hormone replacement therapy in managing hot flashes and menopausal vaginal symptoms in postmenopausal women with a history of node-negative invasive carcinoma or ductal carcinoma in situ of the breast who are receiving adjuvant tamoxifen.
• Determine the effect of this regimen on blood coagulation and lipid profiles in these patients.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior hysterectomy (yes vs no), symptom complex (vasomotor vs vaginal vs both), duration of hot flashes (less than 1 year or no hot flashes vs 1 year or more), and average daily number of hot flashes (less than 10 or none vs 10 or more). Patients are randomized to one of two treatment arms.

• Arm I: Patients who have not undergone prior hysterectomy receive oral medroxyprogesterone once daily for 6 months. If, after 1 month, symptoms do not resolve, patients receive oral conjugated estrogens once daily in addition to medroxyprogesterone for 5 months. Patients who have undergone prior hysterectomy receive oral conjugated estrogens once daily for 6 months.
• Arm II: Patients receive oral placebo once daily for 6 months. Quality of life is assessed at baseline and months 1, 2, 3, and 6.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study within 12 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Chicago, Illinois, United States, 60611
      • Veterans Affairs Medical Center - Lakeside Chicago
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis (Roudebush)
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • CCOP - Missouri Valley Cancer Consortium
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Comprehensive Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37212
      • Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Comprehensive Cancer Center
    • Madison, Wisconsin, United States, 53705
      • Veterans Affairs Medical Center - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed node-negative invasive carcinoma or ductal carcinoma in situ of the breast
• No contralateral breast cancer
• No recurrent or metastatic disease
• Completion of active non-hormonal therapy for breast cancer
• Receiving tamoxifen (20 mg/day) for at least 3 months prior to study and plan to continue drug while on study
• Hot flashes severe enough to seek medical intervention (at least 7-8 moderate to severe hot flashes per day or 60 per week at baseline) AND/OR
• Vaginal symptoms, including dyspareunia, vaginal dryness, irritation, or thinning due to estrogen deficiency
• If uterus present, no prior histologically confirmed adenomatous or atypical endometrial hyperplasia or endometrial carcinoma AND no concurrent endometrial cancer confirmed by pelvic exam within the past year
• No active endometriosis
• No unexplained vaginal bleeding

• Hormone receptor status:

  • Estrogen and progesterone receptor status known for patients with invasive breast cancer

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Postmenopausal
• No menstrual period for more than 12 months OR prior bilateral oophorectomy
• Must be over 55 years of age OR have documented follicle-stimulating hormone levels in postmenopausal range if one or both ovaries remain after prior hysterectomy

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No prior superficial or deep venous or arterial thrombosis
• No serious venous stasis disease

Pulmonary:

• No pulmonary embolus

Other:

• Must be able to read and speak English
• No lower extremity trauma, swelling, or tenderness within the past 4 weeks
• No active gallbladder disease
• No migraine headaches
• No other prior malignancy unless curatively treated with no evidence of recurrence
• No concurrent seizure disorder requiring anti-seizure medication

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• See Disease Characteristics
• No other concurrent estrogen or hormone replacement therapy
• No concurrent clonidine, bellergal, progestational agent, or methyldopa for hot flashes
• No concurrent topical vaginal estrogen cream (e.g., Estring or Vagifem) for patients with vaginal symptoms only

Radiotherapy:

• Not specified

Surgery:

• At least 4 weeks since prior surgery

Other:

• At least 12 months since prior treatment for congestive heart failure
• Concurrent selective serotonin reuptake inhibitors (SSRI) or antidepressants with SSRI activity allowed if begun at least 3 months prior to study and continue during study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Masking: Double

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Melody A. Cobleigh, MD, Rush University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2000
• Primary Completion (Actual): August 1, 2002
• Study Completion (Actual): June 15, 2007

Study Registration Dates

• First Submitted: November 9, 2001
• First Submitted That Met QC Criteria: September 16, 2003
• First Posted (Estimated): September 17, 2003

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer; menopausal symptoms; breast cancer in situ; hot flashes; ductal breast carcinoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hot Flashes; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Estrogens; Medroxyprogesterone Acetate; Medroxyprogesterone; Estrogens, Conjugated (USP)
• Other Study ID Numbers: CDR0000069015; E-2193; NCI-P01-0194