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

NCT ID: NCT04335682

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

111 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-17

Study Completion Date

2026-08-31

Brief Summary

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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

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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).

Conditions

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Metastatic Prostate Cancer Prostate Cancer Metastatic Prostate Cancer Castrate Resistant Prostate Cancer Hormone Sensitive Prostate Cancer Non-metastatic Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Darolutamide (DARO)

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.

Group Type ACTIVE_COMPARATOR

Darolutamide

Intervention Type DRUG

Patients randomized to darolutamide.

Enzalutamide (ENZ)

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.

Group Type ACTIVE_COMPARATOR

Enzalutamide

Intervention Type DRUG

Patients randomized to enzalutamide.

Interventions

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Darolutamide

Patients randomized to darolutamide.

Intervention Type DRUG

Enzalutamide

Patients randomized to enzalutamide.

Intervention Type DRUG

Other Intervention Names

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Nubeqa Xtandi

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Alliance Foundation Trials, LLC.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evanthia Galanis, MD

Role: PRINCIPAL_INVESTIGATOR

Alliance Foundation Trials

Locations

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University of California - San Francisco at Mount Zion

San Francisco, California, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Cancer Center

Fairway, Kansas, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Other Identifiers

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AFT-47

Identifier Type: -

Identifier Source: org_study_id

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