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