Castrate Resistant Prostate Cancer, Hormone Sensitive Prostate Cancer, Metastatic Prostate Cancer, Non-metastatic Prostate Cancer, Prostate Cancer, Prostate Cancer Metastatic
Conditions
Brief summary
This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with metastatic and non-metastatic castration resistant prostate cancer (CRPC) or metastatic hormone sensitive prostate cancer (HSPC). 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).
Interventions
DRUGDarolutamide
Patients randomized to darolutamide.
DRUGEnzalutamide
Patients randomized to enzalutamide.
Sponsors
Alliance Foundation Trials, LLC.
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria include: * Histologically or cytologically confirmed adenocarcinoma of the prostate * Progressive disease per PCWG3 criteria with EITHER: Metastatic CRPC or non- metastatic CRPC (M0CRPC) * For mCRPC: metastatic disease documented by standard or novel imaging techniques * OR for M0CPRC: no evidence of metastatic disease on standard imaging. * OR mHSPC * Surgically or medically castrated, with testosterone levels of \<50 ng/dL. If the patient is medically castrated, continuous dosing with GnRH agonist or antagonist must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * Able to complete cognitive testing and patient reported outcome surveys in English. * Ability to swallow study medications whole. * Able to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Proportion of impaired patients | 24 weeks | Cumulative proportion of impaired patients in each arm |
| Change in lowest ranking domain | 24 weeks | Average change in lowest ranking domain Cambridge Neuropsychological Test Automated Battery \[CANTAB\] questionnaire 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. |
| 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. |
| 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. |
| 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%) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREvanthia Galanis, MD
Alliance Foundation Trials
Outcome results
None listed