RATIONALE: Venlafaxine may be effective in relieving hot flashes caused by hormone therapy. Giving venlafaxine with zolpidem (a sleeping pill) may improve sleep and quality of life in women who are receiving hormone therapy for treatment or prevention of breast cancer.

PURPOSE: This randomized clinical trial is studying giving venlafaxine together with zolpidem to see how well it works compared to venlafaxine alone in relieving hot flashes and associated sleep disorders in women who are receiving hormone therapy to treat or prevent breast cancer.

Condition	Treatment or Intervention
Breast Cancer Hot Flashes Sleep Disorders	Drug: venlafaxine  Drug: zolpidem  Procedure: complications of therapy assessment/management  Procedure: hot flashes attenuation  Procedure: menopausal symptoms attenuation  Procedure: sleep disorders therapy  Procedure: supportive care/therapy

Further Study Details: 

OBJECTIVES:

• Compare the effect of venlafaxine with vs without zolpidem on sleep continuity in women who experience hot flushes and associated sleep disorders who are at high risk for developing breast cancer.
• Compare quality of life in patients treated with these drugs.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified by concurrent use of serotonin-reuptake inhibitors (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (venlafaxine and placebo): Patients receive oral venlafaxine or other SRI once daily and oral placebo once daily for 5 weeks*.
• Arm II (venlafaxine and zolpidem): Patients receive oral venlafaxine or other SRI once daily and oral zolpidem once daily for 5 weeks*. NOTE: *After 5 weeks of study treatment, patients in arms I and II may taper or continue venlafaxine over 2 weeks (for a total duration of venlafaxine use of 7 weeks); patients in arm II may taper or continue zolpidem over 1 week (for a total duration of zolpidem use of 6 weeks); continuation or tapering of drugs in both arms occurs in an open-label fashion off study.

Treatment in both arms continues in the absence of unacceptable toxicity.

In both arms, hot flushes, sleep continuity, sleep quality, and quality of life are assessed at baseline and at weeks 1, 3, and 6.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this study within 20 months.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• At increased risk of developing breast cancer, meeting 1 of the following criteria:
• Diagnosis of 1 of the following:
• Ductal carcinoma in situ
• Invasive breast cancer
• Lobular carcinoma in situ
• Atypical ductal or lobular hyperplasia
• Lobular carcinoma
• Candidate for breast cancer risk reduction for any of the following:
• Predisposing mutation in a breast cancer susceptibility gene
• Prior chest radiotherapy for Hodgkin's disease
• Gail model score > 1.67% over 5 years
• Experiencing daytime and nocturnal hot flushes at least 14 times per week within the past 2 weeks
• Experiencing sleep disturbance, characterized by the presence of all of the following for ≥ 1 month:
• ≥ 3 awakenings per night occurring ≥ 3 nights per week
• Insomnia impedes daytime function
• Hot flushes are the primary cause of insomnia (determined at baseline visit)
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 to 65

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No clinically significant cardiac disease
• No uncontrolled hypertension within the past 3 months, defined as the following:
• Diastolic blood pressure > 95 mm Hg on > 1 occasion
• Systolic blood pressure > 160 mm Hg on > 1 occasion

Pulmonary

• No clinically significant respiratory disease

Psychiatric

• Beck depression inventory score ≤ 15
• No active panic or depressive disorder within the past month
• No lifetime history of bipolar or psychotic disorder
• No active substance-use disorders, including alcohol and benzodiazepines, within the past year
• No suicidal or homicidal ideation
• No hypomania or mania

Other

• No prior adverse reaction to venlafaxine or zolpidem
• None of the following sleep disorders within the past 6 months:
• Sleep apnea
• Narcolepsy
• Periodic limb movement disturbance
• No abuse or misuse of study medication
• No daytime sedation that interferes with ability to function
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 1 month after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 3 months since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• More than 1 month since prior regular use (> 25% of the time) of oral, transdermal, or injection preparations of androgens, estrogens, or progestins
• Vaginal suppositories and creams allowed
• No concurrent regular use of oral, transdermal, or injection preparations of androgens, estrogens, or progestins

Radiotherapy

• See Disease Characteristics
• More than 3 months since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 1 month since prior regular use (> 25% of the time) of any of the following:
• Hypnotic agents (e.g., benzodiazepines, zolpidem, zaleplon, trazodone, or diphenhydramine)
• Clonidine
• More than 1 month since prior antidepressants or other medications that are known to influence mood > 25% of the time (no serotonin-reuptake inhibitors [SRI] stratum only)
• Concurrent SRI allowed provided they were initiated ≥ 1 month ago at or above the minimum dose, including any of the following (SRI stratum only):
• Fluoxetine
• Paroxetine
• Paroxetine CR
• Sertraline
• Citalopram
• S-citalopram
• Venlafaxine
• Fluvoxamine
• No concurrent warfarin
• No concurrent hypnotic agents, clonidine, or antidepressants, or other medications known to influence sleep, or mood

Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115-6084,  United States; Recruiting
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States; Recruiting

Study chairs or principal investigators

Hadine Joffe, MD, MSC,  Study Chair,  Massachusetts General Hospital   

Study ID Numbers:  CDR0000365502; MGH-DFCI-02311; DFCI-02311; NCT00084669
Record last reviewed:  August 2004
Last Updated:  April 5, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084669
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08