Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Supportive care Closed 18 to 65 Other MGH-DFCI-02311 DFCI-02311, NCT00084669

Objectives

1. 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.
2. Compare quality of life in patients treated with these regimens.

Entry 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

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

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

Expected Enrollment

A total of 119 patients will be accrued for this study within 20 months.

Outcomes

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

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

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.

Trial Contact Information

Trial Lead Organizations

Massachusetts General Hospital

Hadine Joffe, MD, MSC, Protocol chair		Ph: 617-724-1849; 877-726-5130

Registry Information
Official Title		Targeting Insomnia to Enhance Hot Flush Treatment in Women Receiving Therapy for Breast Cancer or Breast Cancer Risk-Reduction
Trial Start Date		2004-05-26
Registered in ClinicalTrials.gov		NCT00084669
Date Submitted to PDQ		2004-04-02
Information Last Verified		2008-11-30

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