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Completed

NCT Number: NCT04335682

Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide

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.

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Key information

Conditions

Metastatic Prostate Cancer Castrate Resistant Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Hormone Sensitive Prostate Cancer Male Urogenital Diseases Neoplasms Neoplasms by Site Non-Metastatic Prostate Cancer Prostate Cancer Prostate Cancer Metastatic Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

University of California - San Francisco at Mount Zion, San Francisco, California, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Darolutamide

Drug

Patients randomized to darolutamide.

Other names: Nubeqa

Enzalutamide

Drug

Patients randomized to enzalutamide.

Other names: Xtandi

Primary outcomes

  1. Change in the maximally changed cognitive domain

    Time frame: 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 outcomes

  1. Crossover from enzalutamide to darolutamide and darolutamide to enzalutamide

    Time frame: 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.

  2. Maximally changed cognitive domain

    Time frame: 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.

  3. Proportion of impaired patients

    Time frame: 24 weeks

    Cumulative proportion of impaired patients in each arm

  4. Proportion of impaired patients

    Time frame: 48 weeks

    Cumulative proportion of impaired patients in each arm

  5. Change in lowest ranking domain

    Time frame: 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.

  6. Change in lowest ranking domain

    Time frame: 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.

  7. Improve in cognitive function after crossover

    Time frame: 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.

  8. Prostate-specific antigen (PSA) progression.

    Time frame: 104 weeks

    Estimation of the probability of PSA progression over time using the cumulative incidence function.

  9. Progression free survival

    Time frame: 104 weeks

    Progression-free survival will be evaluated for each cohort.

  10. Prostate-specific antigen (PSA) response rate

    Time frame: 24 weeks

    Estimation or the proportion PSA responses at 24 weeks (on the basis of a decrease from baseline of ≥ 50%)

Sponsors and collaborators

Lead sponsor

Alliance Foundation Trials, LLC.

Other

Collaborators

  • Bayer

Registry information

Official study title

A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)

Acronym: ARACOG

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Apr 6, 2020
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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