Testing the Effects of Oxybutynin for the Treatment of Hot Flashes in Men Receiving Hormone Therapy for Prostate Cancer

Phase 2

Completed

Conditions: Prostate Carcinoma

Interventions: Drug: Placebo Administration
Drug: Oxybutynin Chloride
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT04600336

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: This phase II trial compares the effect of oxybutynin versus placebo for reducing hot flashes in men receiving androgen deprivation (hormone) therapy for the treatment of prostate cancer . Androgen deprivation therapy decreases testosterone and other androgens through medications or surgical removal of the testicles. Relative to placebo, low- or high-dose oxybutynin may reduce hot flashes in men receiving androgen deprivation therapy.

Detailed Description: The primary and secondary objectives of the study:

PRIMARY OBJECTIVE:

I. To assess the effects of two doses of oxybutynin chloride (oxybutynin) on hot flash scores relative to placebo.

SECONDARY OBJECTIVES:

I. To assess study accrual rates and compliance with the therapy. II. To characterize the safety and adverse event profile of two doses of oxybutynin in the study population.

III. To evaluate the consistency of the results across the various methods used to evaluate the efficacy of oxybutynin (i.e., hot flash scores versus hot flash frequencies, mean differences versus 50% or greater reduction since baseline, single day versus full week to define patients' baseline hot flash scores).

IV. To compare patient-reported quality of life and hot flash interference, as measured by the Hot Flash Related Daily Interference Scale (HFRDIS), across arms.

V. To compare other changes in patient symptoms, as measured by the Symptom Experience Questionnaire, across arms.

OUTLINE: Patients are randomized to 1 of 4 arms in a 2:2:1:1 ratio according to the dynamic allocation scheme.

Experimental Arm (low dose): Patients receive low-dose oxybutynin chloride orally (PO) twice daily (BID) on days 8-49 (6 weeks) in the absence of unacceptable toxicity.

Experimental Arm (high dose): Patients receive high-dose oxybutynin chloride PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.

Placebo Arm (low dose): Patients receive low-dose placebo PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to Experimental Arm (low dose) per physician discretion.

Placebo Arm (high dose): Patients receive high-dose placebo PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to Experimental Arm (high dose) per physician discretion.

There will be a 6-week follow-up for the Placebo Arm patients who participate in the optional crossover phase.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 88

Inclusion Criteria

Men who are currently receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. ADT is defined by a history of orchiectomy, or ongoing usage of gonadotropin-releasing hormone agonists or antagonists. Men receiving abiraterone, but not enzalutamide, apalutamide, and darolutamide are eligible, as the latter three are metabolized by CYP3A4 and may affect oxybutynin serum concentrations.
Patients must be on a stable dose of all hormone-directed therapies for at least 28 days prior to registration and must not be planning to discontinue this therapy for at least 42 days following registration. Patients receiving radiation therapy during the study period are eligible
Eligible patient must have bothersome hot flashes for >= 14 days prior to registration, defined by an occurrence of >= 28 times per week and of sufficient severity to cause the patient to seek therapeutic intervention
Life expectancy of greater than 6 months
Eastern Cooperative Oncology Group (ECOG) performance status - 0, 1, or 2
In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English

Exclusion Criteria

No current use or future planned use of any of the following agents during the study period: drugs that are not Food and Drug Administration (FDA) approved for use in humans, androgens, estrogens, progesterone analogs, gabapentin, selective serotonin reuptake inhibitor (SSRI)/serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressants, cholinergic agonists, cholinesterase inhibitors, or complementary/alternative medicine taken for the purpose of managing hot flashes. Prior use of these agents is permitted as long as they are discontinued before registration
No current or prior use of oxybutynin
Patients with a history of any of the following contraindications to oxybutynin are not eligible: gastroparesis or gastrointestinal obstructive disorders; significant gastric reflux symptoms not controlled by medication; ulcerative colitis; narrow-angle glaucoma; urinary retention requiring indwelling or intermittent self-catheterization within the prior 6 months; hypersensitivity to oxybutynin or any other components of the product; current uncontrolled hyperthyroidism; uncontrolled coronary artery disease or a history of myocardial infarction within the prior 12 months; New York Heart Association (NYHA) class II-IV congestive heart failure; symptomatic cardiac arrhythmias; current uncontrolled hypertension; myasthenia gravis; or dementia

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
high-dose oxybutynin chloride	Quality-of-Life Assessment	Patients receive high-dose oxybutynin chloride (5.0 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.
low-dose oxybutynin	Quality-of-Life Assessment	Patients receive low-dose oxybutynin chloride (2.5 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.
high-dose oxybutynin chloride	Questionnaire Administration	Patients receive high-dose oxybutynin chloride (5.0 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.
low-dose placebo	Placebo Administration	Patients receive a low-dose placebo (2.5 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - low-dose oxybutynin per physician discretion.
high-dose placebo	Quality-of-Life Assessment	Patients receive a high-dose placebo (5.0 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - high-dose oxybutynin chloride per physician discretion.
high-dose placebo	Questionnaire Administration	Patients receive a high-dose placebo (5.0 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - high-dose oxybutynin chloride per physician discretion.
low-dose placebo	Questionnaire Administration	Patients receive a low-dose placebo (2.5 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - low-dose oxybutynin per physician discretion.
low-dose oxybutynin	Questionnaire Administration	Patients receive low-dose oxybutynin chloride (2.5 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.
low-dose placebo	Quality-of-Life Assessment	Patients receive a low-dose placebo (2.5 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - low-dose oxybutynin per physician discretion.
high-dose placebo	Placebo Administration	Patients receive a high-dose placebo (5.0 mL twice daily) PO BID on days 8-49 (6 weeks). After 6 weeks, patients may cross over to experimental arm - high-dose oxybutynin chloride per physician discretion.
low-dose oxybutynin	Oxybutynin Chloride	Patients receive low-dose oxybutynin chloride (2.5 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.
high-dose oxybutynin chloride	Oxybutynin Chloride	Patients receive high-dose oxybutynin chloride (5.0 mL twice daily) PO BID on days 8-49 (6 weeks) in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Change in Weekly Patient-reported Hot Flash Scores	6 weeks post-randomization	Using patients' hot flash diaries, daily hot flash scores will be determined by multiplying the frequency of each defined hot flash grade (mild=1, moderate=2, severe=3, very severe=4) by the severity and summing the values over a 24-hour period. Weekly hot flash scores will be computed by averaging these hot flash scores across 7 days. A score of 0 would mean the patient experienced no hot flashes during the week, and every unit increase reflects more or more severe hot flashes experienced. A mixed model will be estimated that includes baseline and weekly hot flash scores across the 6-week treatment period. Estimates from the mixed model will be used to construct 90% confidence intervals for mean differences in hot flash score reduction from baseline to 6 weeks between the oxybutynin and placebo arms. Contrasts estimated via the mixed model will involve a two-sided t-test with alpha = .10.

Secondary Outcome Measures

Name	Time	Method
Patient-reported Symptoms	6 weeks post-randomization	Patient-reported symptoms will be assessed by the Symptom Experience Questionnaire. A mixed model will be estimated that includes baseline and weekly patient-reported symptoms across the 6-week treatment period. The mean change in answers from baseline to week 6 to the item "How Distressing Was Your Experience With Hot Flashes" will be reported. Answers are given on a scale from 0 to 10 with higher scores being worse; therefore a positive number indicates a worse experience at week 6.
Change in Patient-reported Hot Flash Frequency	6 weeks post-randomization	Weekly hot flash frequencies will be determined by patients' hot flash diaries. A mixed model will be estimated that includes baseline and weekly hot flash frequencies across the 6-week treatment period. The mixed model and subsequent contrasts will account for the observed distribution of weekly hot flash frequencies.
Number of Patients That Experienced a Grade 3+ Adverse Event	12 weeks post-randomization	Grade 3 or higher adverse events will be assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 and summarized by arm.
Patients That Completed Treatment	4 months	Treatment adherence rates will be calculated by dividing the number of patients who completed treatment per protocol by the number of patients who started treatment. Treatment adherence rates will be summarized by arm.
Patient-reported Hot Flash Interference	6 weeks post-randomization	A mixed model will be estimated that includes patients' scores on the Hot Flash Related Daily Interference Scale (HFRDIS) across the 6-week treatment period. The mean change in answers from baseline to week 6 to the item "Overall Quality of Life" will be reported. Answers are given on a scale from 0 to 10 with higher scores being worse; therefore a positive number indicates a worse experience at week 6.
Patient Accrual	26 months	The time required to accrue 87 patients will be reported.

Trial Locations

Locations (103): Arizona Breast Cancer Specialists-Gilbert
🇺🇸
Gilbert, Arizona, United States
Arizona Center for Cancer Care-Peoria
🇺🇸
Peoria, Arizona, United States
Cancer Center at Saint Joseph's
🇺🇸
Phoenix, Arizona, United States
Arizona Breast Cancer Specialists-Phoenix
🇺🇸
Phoenix, Arizona, United States
Arizona Breast Cancer Specialists
🇺🇸
Scottsdale, Arizona, United States
Arizona Breast Cancer Specialists-Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Arizona Center for Cancer Care-Surprise
🇺🇸
Surprise, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
Fremont - Rideout Cancer Center
🇺🇸
Marysville, California, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
🇺🇸
Truckee, California, United States
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Arizona Breast Cancer Specialists-Gilbert
🇺🇸Gilbert, Arizona, United States