Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide
- Conditions
- Hormone Sensitive Prostate CancerProstate Cancer MetastaticNon-metastatic Prostate CancerMetastatic Prostate CancerProstate CancerCastrate Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT04335682
- Lead Sponsor
- Alliance Foundation Trials, LLC.
- Brief Summary
This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with non-metastatic and metastatic castration-resistant prostate cancer (mCRPC or M0CRPC) treated with darolutamide or enzalutamide. Approximately 132 patients will be enrolled. Eligible patients will be randomized in a 1:1 fashion to treatment with enzalutamide 160 mg orally daily or darolutamide 600 mg orally twice daily, in combination with standard LHRH agonist based treatment. Cognitive assessments will be performed using modules from Cambridge Neuropsychological Test Automated Battery (CANTAB) an internationally recognized software for assessing cognitive function and impairment.
- Detailed Description
The goal of the trial is to assess cognitive and quality of life outcomes over the 48-week primary data collection period of the trial. This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with Advanced prostate cancer: metastatic and non-metastatic castration resistant prostate cancer (CRPC) or metastatic hormone sensitive prostate cancer (HSPC).
The primary endpoint will be the percent change in the maximally changed cognitive domain by 24 weeks in each study arm. Patients will be stratified by age (\<65, 65-80, \> 80). Patients will be allowed to cross over from either treatment to the opposite treatment arm at 12 and 24 weeks if they meet any of the cross-over criteria as described in the protocol.
Cognitive assessments will be performed using Cambridge Neuropsychological Test Automated Battery (CANTAB), an internationally recognized software for assessing cognitive function and impairment. Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
Blood samples will be collected for exploratory genomic analyses (AR CAG repeat length, PHS, exosome analysis).
Patients will have the option to opt into an additional separate MRI sub-study. A subset of 40 patients (20 per arm) will undergo fMRI to measure percent signal change in the HP PFC circuit at baseline, 24 and 48 weeks or/and cross-over/end of treatment visit (if applicable).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 111
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Darolutamide (DARO) Darolutamide Patients will take DARO at a dose of 600 mg (300 mg ×2 tablets) by mouth twice daily beginning on Day 1, of Week 1. Patients will take DARO throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy. Enzalutamide (ENZ) Enzalutamide Patients will take ENZ at a dose of 160 mg PO once daily (QD), beginning on Day 1, of Week 1. Patients will take ENZ throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy.
- Primary Outcome Measures
Name Time Method Change in the maximally changed cognitive domain 24 weeks To compare the effects of treatment with enzalutamide (ENZ) versus darolutamide (DARO) on the cognitive function of men with non-metastatic and metastatic castration-resistant prostate cancer by comparing the change in the maximally changed cognitive domain utilizing Cambridge Neuropsychological Test Automated Battery \[CANTAB\] cognitive tests from baseline in patients in each study arm.Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
- Secondary Outcome Measures
Name Time Method Proportion of impaired patients 48 weeks Cumulative proportion of impaired patients in each arm
Improve in cognitive function after crossover 48 weeks Improvement in cognitive function after crossover from each treatment arm based on Cambridge Neuropsychological Test Automated Battery \[CANTAB\] modules. Tests in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time.
Crossover from enzalutamide to darolutamide and darolutamide to enzalutamide 48 weeks Proportion of patients crossing over from each treatment arm based on subjective (self-reported, FACT-Cognitive Function \[Version 3\], FACT-Cog V3, decline by \>10 points from baseline score) cognitive effects.
* Proportion of patients crossing over from each treatment arm based on objective cognitive effects (the Cambridge Neuropsychological Test Automated Battery \[CANTAB\] , decline by \> 30% from baseline on any cognitive domain).
* Proportion of patients crossing over from ENZ to DARO based on Timed Up and Go (TUG) times \>12 seconds or 12 seconds or increase from baseline by \>1 second.
* Proportion of patient crossing over due to neurologic toxicity (fatigue) with a preference to cross over (ENZ or DARO) or severe neurological toxicity \[seizures or posterior reversible encephalopathy syndrome PRES\]). Cross over for severe neurologic toxicity is allowed for patients on ENZ only.Change in lowest ranking domain 48 weeks Average change in lowest ranking domain in Cambridge Neuropsychological Test Automated Battery \[CANTAB\] outcomes at baseline (in a given individual). Tests in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time.
Prostate-specific antigen (PSA) response rate 24 weeks Estimation or the proportion PSA responses at 24 weeks (on the basis of a decrease from baseline of ≥ 50%)
Maximally changed cognitive domain 48 weeks Average decline in maximally changed cognitive domain in patients in each arm based on self-reported cognitive tests (Cambridge Neuropsychological Test Automated Battery \[CANTAB\]). Tests in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
Prostate-specific antigen (PSA) progression. 104 weeks Estimation of the probability of PSA progression over time using the cumulative incidence function.
Progression free survival 104 weeks Progression-free survival will be evaluated for each cohort.
Trial Locations
- Locations (8)
University of California - San Francisco at Mount Zion
🇺🇸San Francisco, California, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Kansas Cancer Center
🇺🇸Fairway, Kansas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States