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

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Oxybutynin Versus Placebo for the Treatment of Hot Flashes in Men Receiving Androgen Deprivation Therapy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Placebo Administration; Drug: Oxybutynin Chloride

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bradley J. Stish, MD; Phone Number: 507-538-6120; Email: stish.bradley@mayo.edu

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Arizona Breast Cancer Specialists-Gilbert
    • Peoria, Arizona, United States, 85381
      • Arizona Center for Cancer Care-Peoria
    • Phoenix, Arizona, United States, 85004
      • Cancer Center at Saint Joseph's
    • Phoenix, Arizona, United States, 85027
      • Arizona Breast Cancer Specialists-Phoenix
    • Scottsdale, Arizona, United States, 85258
      • Arizona Breast Cancer Specialists-Scottsdale
    • Scottsdale, Arizona, United States, 85251
      • Arizona Breast Cancer Specialists
    • Surprise, Arizona, United States, 85374
      • Arizona Center for Cancer Care-Surprise
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • California
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
  • Colorado
    • Grand Junction, Colorado, United States, 81505
      • Grand Valley Oncology
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Hawaii Cancer Care - Westridge
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
  • Illinois
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Boone, Iowa, United States, 50036
      • McFarland Clinic - Boone
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic - Trinity Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
  • Michigan
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Tawas City, Michigan, United States, 48764
      • Ascension Saint Joseph Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Burnsville, Minnesota, United States, 55337
      • Minnesota Oncology - Burnsville
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68114
      • Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
  • New Jersey
    • Cape May Court House, New Jersey, United States, 08210
      • AtlantiCare Health Park-Cape May Court House
    • Egg Harbor Township, New Jersey, United States, 08234
      • AtlantiCare Surgery Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Weiler Hospital
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Messino Cancer Centers
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Virginia
    • Martinsville, Virginia, United States, 24115
      • Sovah Health Martinsville
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Appleton, Wisconsin, United States, 54915
      • Ascension Saint Elizabeth Hospital
    • Brookfield, Wisconsin, United States, 53045
      • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
    • Chilton, Wisconsin, United States, 53014
      • Ascension Calumet Hospital
    • Franklin, Wisconsin, United States, 53132
      • Ascension Saint Francis - Reiman Cancer Center
    • Mequon, Wisconsin, United States, 53097
      • Ascension Columbia Saint Mary's Hospital Ozaukee
    • Milwaukee, Wisconsin, United States, 53210
      • Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Hospital - Milwaukee
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center
    • Mukwonago, Wisconsin, United States, 53149
      • ProHealth D N Greenwald Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Oshkosh, Wisconsin, United States, 54904
      • Ascension Mercy Hospital
    • Racine, Wisconsin, United States, 53405
      • Ascension All Saints Hospital
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Ascension Medical Group Southeast Wisconsin - Mayfair Road
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low-dose oxybutynin; 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other: Questionnaire Administration; Ancillary studies; Drug: Oxybutynin Chloride; Given PO
Experimental: high-dose 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other: Questionnaire Administration; Ancillary studies; Drug: Oxybutynin Chloride; Given PO
Placebo Comparator: low-dose placebo; 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO
Placebo Comparator: high-dose placebo; 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported hot flash scores	Using patients' hot flash diaries, daily hot flash scores will be determined by multiplying the frequency of each defined hot flash grade 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 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. At 6 weeks, the proportion of patients who experience a 50% or greater reduction in hot flash scores since baseline will be compared across the oxybutynin and placebo arms using Fisher's exact test or logistic regression.	Baseline up to 6 weeks post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported hot flash frequency	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. At 6 weeks, the proportion of patients who experience a 50% or greater reduction in hot flash frequency since baseline will be compared across the oxybutynin and placebo arms using Fisher's exact test or logistic regression. Consistency of the results will be assessed across the various methods used to evaluate the efficacy of oxybutynin in this trial (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).	Baseline up to 6 weeks post-randomization
Incidence of adverse events	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.	Baseline up to 12 weeks post-randomization
Patient-reported symptoms	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. Estimates from the mixed model will be used to construct 90% confidence intervals for mean differences in patient-reported symptoms between the oxybutynin and placebo arms at 6 weeks. Contrasts estimated via the mixed model will involve a two-sided t-test with alpha = .10.	Baseline and at the end of each week of treatment, assessed up to 6 weeks post-randomization
Patient accrual	The time required to accrue 87 patients will be reported.	Up to 2 years
Treatment adherence rates	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.	Up to 2 years
Patient-reported quality of life: scale	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. Estimates from the mixed model will be used to construct 90% confidence intervals for mean differences in patient-reported quality of life between the oxybutynin and placebo arms at 6 weeks. Contrasts estimated via the mixed model will involve a two-sided t-test with alpha = .10.	Baseline and at the end of each week of treatment, assessed up to 6 weeks post-randomization
Patient-reported hot flash interference	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. Estimates from the mixed model will be used to construct 90% confidence intervals for mean differences in patient-reported hot flash interference between the oxybutynin and placebo arms at 6 weeks. Contrasts estimated via the mixed model will involve a two-sided t-test with alpha = .10.	Baseline and at the end of each week of treatment, assessed up to 6 weeks post-randomization

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Bradley J. Stish, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Hot Flashes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Oxybutynin
• Other Study ID Numbers: A222001; UG1CA189823 (U.S. NIH Grant/Contract); NCI-2020-07169 (Registry Identifier: NCI Clinical Trial Reporting Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No