Clinical trial NCT04600336: Testing the Effects of Oxybutynin for the Treatment of Hot Flashes in Men Receiving Hormone Therapy for Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Carcinoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-10-23
Enrollment: 88
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Weekly Patient-reported Hot Flash Scores
timeFrame: 6 weeks post-randomization
Secondary outcomes:
measure: Change in Patient-reported Hot Flash Frequency
timeFrame: 6 weeks post-randomization
measure: Number of Patients That Experienced a Grade 3+ Adverse Event
timeFrame: 12 weeks post-randomization
measure: Patient-reported Symptoms
timeFrame: 6 weeks post-randomization
measure: Patient Accrual
timeFrame: 26 months
measure: Patients That Completed Treatment
timeFrame: 4 months
measure: Patient-reported Hot Flash Interference
timeFrame: 6 weeks post-randomization
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Arizona Breast Cancer Specialists-Gilbert
state: Arizona
city: Peoria
country: United States
facility: Arizona Center for Cancer Care-Peoria
state: Arizona
city: Phoenix
country: United States
facility: Cancer Center at Saint Joseph's
state: Arizona
city: Phoenix
country: United States
facility: Arizona Breast Cancer Specialists-Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Breast Cancer Specialists
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Breast Cancer Specialists-Scottsdale
state: Arizona
city: Surprise
country: United States
facility: Arizona Center for Cancer Care-Surprise
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center-North Campus
state: Arizona
city: Marysville
country: United States
facility: Fremont - Rideout Cancer Center
state: California
city: Truckee
country: United States
facility: Gene Upshaw Memorial Tahoe Forest Cancer Center
state: California
city: Grand Junction
country: United States
facility: Grand Valley Oncology
state: Colorado
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: 'Aiea
country: United States
facility: Hawaii Cancer Care - Westridge
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc - Waterfront Plaza
state: Hawaii
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: O'Fallon
country: United States
facility: Cancer Care Center of O'Fallon
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic - Boone
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic - Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic - Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic - Marshalltown
state: Iowa
city: Flint
country: United States
facility: Genesee Cancer and Blood Disease Treatment Center
state: Michigan
city: Flint
country: United States
facility: Genesee Hematology Oncology PC
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Saginaw
country: United States
facility: Ascension Saint Mary's Hospital
state: Michigan
city: Saginaw
country: United States
facility: Oncology Hematology Associates of Saginaw Valley PC
state: Michigan
city: Tawas City
country: United States
facility: Ascension Saint Joseph Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Burnsville
country: United States
facility: Minnesota Oncology - Burnsville
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maple Grove
country: United States
facility: Fairview Clinics and Surgery Center Maple Grove
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Monticello
country: United States
facility: Monticello Cancer Center
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology PA-Woodbury
state: Minnesota
city: Wyoming
country: United States
facility: Fairview Lakes Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: MU Health - University Hospital/Ellis Fischel Cancer Center
state: Missouri
city: Rolla
country: United States
facility: Delbert Day Cancer Institute at PCRMC
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Cape May Court House
country: United States
facility: AtlantiCare Health Park-Cape May Court House
state: New Jersey
city: Egg Harbor Township
country: United States
facility: AtlantiCare Surgery Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Weiler Hospital
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: Asheville
country: United States
facility: Messino Cancer Centers
state: North Carolina
city: Clinton
country: United States
facility: Southeastern Medical Oncology Center-Clinton
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center-Goldsboro
state: North Carolina
city: Jacksonville
country: United States
facility: Southeastern Medical Oncology Center-Jacksonville
state: North Carolina
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center
state: North Dakota
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Martinsville
country: United States
facility: Sovah Health Martinsville
state: Virginia
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Appleton
country: United States
facility: Ascension Saint Elizabeth Hospital
state: Wisconsin
city: Brookfield
country: United States
facility: Ascension Southeast Wisconsin Hospital - Elmbrook Campus
state: Wisconsin
city: Chilton
country: United States
facility: Ascension Calumet Hospital
state: Wisconsin
city: Franklin
country: United States
facility: Ascension Saint Francis - Reiman Cancer Center
state: Wisconsin
city: Mequon
country: United States
facility: Ascension Columbia Saint Mary's Hospital Ozaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
state: Wisconsin
city: Milwaukee
country: United States
facility: Ascension Columbia Saint Mary's Hospital - Milwaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Zablocki Veterans Administration Medical Center
state: Wisconsin
city: Mukwonago
country: United States
facility: ProHealth D N Greenwald Center
state: Wisconsin
city: New Richmond
country: United States
facility: Cancer Center of Western Wisconsin
state: Wisconsin
city: Oconomowoc
country: United States
facility: ProHealth Oconomowoc Memorial Hospital
state: Wisconsin
city: Oshkosh
country: United States
facility: Ascension Mercy Hospital
state: Wisconsin
city: Racine
country: United States
facility: Ascension All Saints Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: Wauwatosa
country: United States
facility: Ascension Medical Group Southeast Wisconsin - Mayfair Road
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Bradley J. Stish, MD
role: STUDY_CHAIR
References: