Clinical trial NCT04335682: Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide
Official title: A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Prostate Cancer Metastatic
Prostate Cancer
Castrate Resistant Prostate Cancer
Hormone Sensitive Prostate Cancer
Non-metastatic Prostate Cancer
Lead sponsor: Alliance Foundation Trials, LLC.
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2020-04-06
Enrollment: 111
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

Eligibility 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.

Primary outcomes:
measure: Change in the maximally changed cognitive domain
timeFrame: 24 weeks
Secondary outcomes:
measure: Crossover from enzalutamide to darolutamide and darolutamide to enzalutamide
timeFrame: 48 weeks
measure: Maximally changed cognitive domain
timeFrame: 48 weeks
measure: Proportion of impaired patients
timeFrame: 24 weeks
measure: Proportion of impaired patients
timeFrame: 48 weeks
measure: Change in lowest ranking domain
timeFrame: 24 weeks
measure: Change in lowest ranking domain
timeFrame: 48 weeks
measure: Improve in cognitive function after crossover
timeFrame: 48 weeks
measure: Prostate-specific antigen (PSA) progression.
timeFrame: 104 weeks
measure: Progression free survival
timeFrame: 104 weeks
measure: Prostate-specific antigen (PSA) response rate
timeFrame: 24 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California - San Francisco at Mount Zion
state: California
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Alliance Foundation Trials
name: Evanthia Galanis, MD
role: PRINCIPAL_INVESTIGATOR
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