Oxybutynin Chloride in Managing Hot Flashes

PRIMARY OBJECTIVES:

I. To determine whether oxybutynin chloride (oxybutynin) can diminish hot-flash activity in women with a history of breast cancer or in women who have a concern about taking estrogen for fear of breast cancer.

SECONDARY OBJECTIVES:

I. To perform a dose-response evaluation of two oxybutynin doses. II. To determine the toxicity of oxybutynin in the study population. III. To assess the impact of hot-flash activity on overall quality of life and to examine whether oxybutynin can diminish this impact on quality of life.

OUTLINE: Patients are randomized into 1 of 4 groups.

GROUP I (LOW-DOSE OXUBUTYNIN CHLORIDE): Patients receive lower dose oxybutynin chloride orally (PO) twice a day (BID) on days 8-49 in the absence of unacceptable toxicity.

GROUP II (LOW-DOSE PLACEBO): Patients receive lower dose placebo PO BID on days 8-49 in the absence of unacceptable toxicity.

GROUP III (HIGH-DOSE OXUBUTYNIN CHLORIDE): Patients receive lower dose oxybutynin chloride PO BID on days 8-14 and higher dose oxybutynin chloride on days 15-49 in the absence of unacceptable toxicity.

GROUP IV (HIGH-DOSE PLACEBO): Patients receive lower dose placebo PO BID on days 8-14 and higher dose placebo on days 15-49 in the absence of unacceptable toxicity.

Inclusion criteria

• History of breast cancer, ductal breast carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) (currently without evidence of malignant disease) OR a concern about taking estrogen for fear of breast cancer
• Bothersome hot flashes (defined by their occurrence of >= 28 times per week and of sufficient severity to prompt the patient to seek therapeutic intervention)
• Presence of hot flashes for > 30 days prior to study entry
• Ability to complete questionnaire(s) by themselves or with assistance
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0, 1
• Ability to provide informed written consent
• Life expectancy >= 6 months
• Willing to work with the enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion criteria

• Any of the following current (=< 4 weeks prior) or planned therapies:

• Antineoplastic chemotherapy (anti-HER2 agents allowed)
• Androgens
• Estrogens (any delivery route)
• Progestogens
• Tamoxifen, raloxifene and aromatase inhibitors are allowed, but patient must have been on a constant dose for at least 28 days and must not be expected to stop the medication during the study period
• Selective serotonin reuptake inhibitors (SSRIs)/serotonin?norepinephrine reuptake inhibitors (SNRIs), when being used for hot flash management or other indications such as depression, is allowed, assuming the dose will remain unchanged for the study duration
• Gabapentin/pregabalin, when being used for hot flash management (use for other indications, such as pain, is allowed, assuming the dose will remain unchanged for the study duration)
• Clonidine
• Agents with known potent anticholinergic activity; agents with mild-moderate anticholinergic activity are allowed
• Prior use of oxybutynin during the period in which patient has had hot flashes
• Pregnant women
• Nursing women
• History of any of the following contraindications to oxybutynin:

• Uncontrolled gastroesophageal reflux disease (GERD) despite appropriate therapy; if patient has history of GERD, but symptoms are well-controlled with medical treatment, patient is eligible
• Ulcerative colitis
• Narrow-angle glaucoma
• Urinary retention
• Hypersensitivity to oxybutynin or any other components of the product
• Current uncontrolled hyperthyroidism
• Coronary heart disease (angina or prior myocardial infarction)
• Congestive heart failure
• Symptomatic cardiac arrhythmias
• Current uncontrolled hypertension
• Myasthenia gravis
• Dementia