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”

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 Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Active Control

Study Primary Completion Date: August 2002

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.

Intervention(s) in this Clinical Trial

• Drug: conjugated estrogens
• Drug: medroxyprogesterone

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eastern Cooperative Oncology Group

Overall Clinical Trial Officials and Contacts

Melody A. Cobleigh, MD Study Chair Rush University Medical Center  

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00026286

Study ID Number: CDR0000069015

ClinicalTrials.gov Identifier: NCT00026286

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database