Clinical trial NCT02961790: Oxybutynin Chloride in Managing Hot Flashes
Official title: A Phase III, Double-Blind, Controlled Trial of Oxybutynin in the Management of Hot Flashes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Carcinoma
Ductal Breast Carcinoma In Situ
Hot Flashes
Lobular Breast Carcinoma In Situ
No Evidence of Disease
Lead sponsor: Academic and Community Cancer Research United
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-11-11
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Average Change in Hot Flash Activity Score From Baseline to Week 7 for Low Dose Oxybutynin vs Placebo and for High Dose Oxybutynin vs Placebo
timeFrame: Baseline up to day 49
Secondary outcomes:
measure: Average Change in Hot Flash Score From Week 1 to Week 7 Comparing Low Dose Oxybutynin to Placebo
timeFrame: Baseline up to day 49
measure: Average Change in Hot Flash Score From Week 1 to Week 7 Comparing High Dose Oxybutynin to Placebo
timeFrame: Baseline up to day 49
measure: Average Change of Severity of Stomach Pain/Cramps Symptoms as Measured by the Symptom Experience Questionnaire From Baseline to Week 7 for Low Dose Oxybutynin vs Placebo and for High Dose Oxybutynin vs Placebo
timeFrame: Baseline up to day 49
measure: Average Change of Daily Interference (Work) From Baseline to Week 7 as Measured by the Hot Flash-Related Daily Interference Scale (HFRDIS) Comparing Low Dose Oxybutynin vs Placebo and High Dose Oxybutynin vs Placebo
timeFrame: Baseline up to day 49
measure: Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
timeFrame: Up to 7 weeks
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center NCI Community Oncology Research Program
state: Illinois
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: Edgewood
country: United States
facility: Saint Elizabeth Medical Center South
state: Kentucky
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium NCORP
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cary
country: United States
facility: Waverly Hematology Oncology
state: North Carolina
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Green Bay
country: United States
facility: Saint Vincent Hospital -Green Bay
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
Study officials:
affiliation: Academic and Community Cancer Research United
name: Charles Loprinzi
role: PRINCIPAL_INVESTIGATOR
References: