Clinical trial NCT00026286: Hormone Replacement Therapy for Hot Flashes and/or Vaginal Symptoms in Postmenopausal Women Receiving Tamoxifen for Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Hot Flashes
Menopausal Symptoms
Keywords: stage I breast cancer
stage II breast cancer
breast cancer in situ
ductal breast carcinoma
hot flashes
menopausal symptoms
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-17
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Rush University Medical Center
name: Melody A. Cobleigh, MD
role: STUDY_CHAIR
References: