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.
Brief Title
Testing the Effects of Oxybutynin for the Treatment of Hot Flashes in Men Receiving Hormone Therapy for Prostate Cancer
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.
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.
Completion Date
Completion Date Type
Actual
Conditions
Prostate Carcinoma
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
* 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
Inclusion 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
* 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
Gender
Male
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04600336
Org Class
Other
Org Full Name
Alliance for Clinical Trials in Oncology
Org Study Id
A222001
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Change in Weekly Patient-reported Hot Flash Scores
Outcome Time Frame
6 weeks post-randomization
Secondary Ids
Secondary Id
UG1CA189823
Secondary Id
NCI-2020-07169
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
6 weeks post-randomization
Outcome Measure
Change in Patient-reported Hot Flash Frequency
Outcome Description
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.
Outcome Time Frame
12 weeks post-randomization
Outcome Measure
Number of Patients That Experienced a Grade 3+ Adverse Event
Outcome Description
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.
Outcome Time Frame
6 weeks post-randomization
Outcome Measure
Patient-reported Symptoms
Outcome Description
The time required to accrue 87 patients will be reported.
Outcome Time Frame
26 months
Outcome Measure
Patient Accrual
Outcome Description
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.
Outcome Time Frame
4 months
Outcome Measure
Patients That Completed Treatment
Outcome Description
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.
Outcome Time Frame
6 weeks post-randomization
Outcome Measure
Patient-reported Hot Flash Interference
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404