Venlafaxine With or Without Zolpidem in Treating Hot Flashes and Associated Sleep Disorders in Women With Breast Cancer OR at High Risk for Developing Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Compare the effect of venlafaxine or another serotonin-reuptake inhibitor with vs without zolpidem, in terms of sleep continuity, in women with breast cancer or at high risk for developing breast cancer who experience hot flushes and associated sleep disorders. Compare quality of life in patients treated with these regimens. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified by concurrent use of serotonin-reuptake inhibitors (SRI). Stratum 1 (no concurrent SRI): Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral venlafaxine once daily and oral zolpidem once daily for 5 weeks*. Arm II: Patients receive oral venlafaxine once daily and oral placebo once daily for 5 weeks*. Stratum 2 (concurrently on SRI): Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral zolpidem once daily for 5 weeks*. Arm II: Patients receive oral placebo once daily for 5 weeks*. NOTE: *After 5 weeks of study treatment, patients in stratum 1 may taper or continue venlafaxine over 2 weeks (for a total duration of venlafaxine use of 7 weeks); patients in arm I of both strata 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. In both strata, treatment continues in the absence of unacceptable toxicity. In both strata, 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 119 patients will be accrued for this study within 20 months.

Official Title
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Targeting Insomnia to Enhance Hot Flush Treatment in Women Receiving Therapy for Breast Cancer or Breast Cancer Risk-Reduction

Conditions
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Breast Cancer, Hot Flashes, Sleep Disorders

Intervention / Treatment
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* Drug: venlafaxine
* Drug: zolpidem tartrate
* Procedure: management of therapy complications


Participation Criteria
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Eligibility Criteria
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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 required provided they were initiated ≥ 1 month ago at or above the minimum dose, including any of the following (concurrent 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: venlafaxine|nan|
|Drug: zolpidem tartrate|nan|
|Procedure: management of therapy complications|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep improvement by biologic data and actigraphy data at the end of study treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life by BDI, QOLI, PSI, NCCTG symptom diary, PSQI, MOS SF-36 at the end of study treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hot flashes, sleep disorders, ductal breast carcinoma in situ, breast cancer in situ, lobular breast carcinoma in situ, lobular breast carcinoma, recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer