Testing the Effects of Oxybutynin for the Treatment of Hot Flashes in Men Receiving Hormone Therapy for Prostate Cancer
- Conditions
- Prostate Carcinoma
- Interventions
- Drug: Placebo AdministrationOther: Quality-of-Life AssessmentOther: 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
- 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
- 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 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-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.
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
Grand Valley Oncology
🇺🇸Grand Junction, Colorado, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Hawaii Cancer Care - Westridge
🇺🇸'Aiea, Hawaii, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸Honolulu, Hawaii, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
Genesee Cancer and Blood Disease Treatment Center
🇺🇸Flint, Michigan, United States
Genesee Hematology Oncology PC
🇺🇸Flint, Michigan, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Ascension Saint Mary's Hospital
🇺🇸Saginaw, Michigan, United States
Oncology Hematology Associates of Saginaw Valley PC
🇺🇸Saginaw, Michigan, United States
Ascension Saint Joseph Hospital
🇺🇸Tawas City, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
🇺🇸Omaha, Nebraska, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
AtlantiCare Health Park-Cape May Court House
🇺🇸Cape May Court House, New Jersey, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
AtlantiCare Surgery Center
🇺🇸Egg Harbor Township, New Jersey, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
Messino Cancer Centers
🇺🇸Asheville, North Carolina, United States
Montefiore Medical Center-Weiler Hospital
🇺🇸Bronx, New York, United States
NYP/Weill Cornell Medical Center
🇺🇸New York, New York, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸Clinton, North Carolina, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸Goldsboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸Jacksonville, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Altru Cancer Center
🇺🇸Grand Forks, North Dakota, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sovah Health Martinsville
🇺🇸Martinsville, Virginia, United States
Ascension Saint Elizabeth Hospital
🇺🇸Appleton, Wisconsin, United States
Ascension Southeast Wisconsin Hospital - Elmbrook Campus
🇺🇸Brookfield, Wisconsin, United States
Ascension Calumet Hospital
🇺🇸Chilton, Wisconsin, United States
Ascension Saint Francis - Reiman Cancer Center
🇺🇸Franklin, Wisconsin, United States
Ascension Columbia Saint Mary's Hospital Ozaukee
🇺🇸Mequon, Wisconsin, United States
Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
🇺🇸Milwaukee, Wisconsin, United States
Ascension Columbia Saint Mary's Hospital - Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
Zablocki Veterans Administration Medical Center
🇺🇸Milwaukee, Wisconsin, United States
ProHealth D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸Oconomowoc, Wisconsin, United States
Ascension Mercy Hospital
🇺🇸Oshkosh, Wisconsin, United States
Ascension All Saints Hospital
🇺🇸Racine, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Ascension Medical Group Southeast Wisconsin - Mayfair Road
🇺🇸Wauwatosa, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States