Oxybutynin Chloride in Managing Hot Flashes
Oxybutynin Chloride in Managing Hot Flashes
This randomized phase III trial studies how well oxybutynin chloride works in managing hot
 flashes in patients who are not candidates for, or not interested in hormone replacement
 therapy. Previous studies have shown that oxybutynin is effective in managing hot flashes,
 however doses used in prior studies have resulted in side effects. This trial is evaluating
 lower doses of oxybutynin with the goal of determining if they are efficacious with less side
 effects.

 ADAM-VTE
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