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

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.

Study Type: Interventional

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

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.

Intervention(s) in this Clinical Trial

• Drug: venlafaxine
• Drug: zolpidem tartrate
• Procedure: management of therapy complications

Primary Measures

• Sleep improvement by biologic data and actigraphy data at the end of study treatment

Secondary Measures

• Quality of life by BDI, QOLI, PSI, NCCTG symptom diary, PSQI, MOS SF-36 at the end of study treatment

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Massachusetts General Hospital

Overall Clinical Trial Officials and Contacts

Hadine Joffe, MD, MSC Study Chair Massachusetts General Hospital  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00084669

Study ID Number: CDR0000365502

ClinicalTrials.gov Identifier: NCT00084669

Health Authority: Unspecified

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