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

NCT04335682 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AFT-47
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in the maximally changed cognitive domain

  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.

  24 weeks

Secondary Outcomes (10)

• Crossover from enzalutamide to darolutamide and darolutamide to enzalutamide

  48 weeks

• Maximally changed cognitive domain

  48 weeks

• Proportion of impaired patients

  24 weeks

• Proportion of impaired patients

  48 weeks

• Change in lowest ranking domain

  24 weeks

Study Arms (2)

Darolutamide (DARO)

ACTIVE COMPARATOR

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.

Drug: Darolutamide

Enzalutamide (ENZ)

ACTIVE COMPARATOR

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.

Drug: Enzalutamide

Interventions

Darolutamide DRUG

Patients randomized to darolutamide.

Also known as: Nubeqa

Darolutamide (DARO)

Enzalutamide DRUG

Patients randomized to enzalutamide.

Also known as: Xtandi

Enzalutamide (ENZ)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Bayer: collaborator

Study Sites (8)

University of California - San Francisco at Mount Zion

San Francisco, California, 94115, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (12)

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• Wang L, Apple AC, Schroeder MP, Ryals AJ, Voss JL, Gitelman D, Sweet JJ, Butt ZA, Cella D, Wagner LI. Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls. Cancer. 2016 Jan 15;122(2):258-68. doi: 10.1002/cncr.29737. Epub 2015 Oct 20.

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• de Souza JA, Yap BJ, Wroblewski K, Blinder V, Araujo FS, Hlubocky FJ, Nicholas LH, O'Connor JM, Brockstein B, Ratain MJ, Daugherty CK, Cella D. Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST). Cancer. 2017 Feb 1;123(3):476-484. doi: 10.1002/cncr.30369. Epub 2016 Oct 7.

  PMID: 27716900 BACKGROUND

• Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. doi: 10.1056/NEJMoa1800536.

  PMID: 29949494 BACKGROUND

• Evans CP, Higano CS, Keane T, Andriole G, Saad F, Iversen P, Miller K, Kim CS, Kimura G, Armstrong AJ, Sternberg CN, Loriot Y, de Bono J, Noonberg SB, Mansbach H, Bhattacharya S, Perabo F, Beer TM, Tombal B. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer. Eur Urol. 2016 Oct;70(4):675-683. doi: 10.1016/j.eururo.2016.03.017. Epub 2016 Mar 19.

  PMID: 27006332 BACKGROUND

• Lim YY, Pietrzak RH, Ellis KA, Jaeger J, Harrington K, Ashwood T, Szoeke C, Martins RN, Bush AI, Masters CL, Rowe CC, Villemagne VL, Ames D, Darby D, Maruff P. Rapid decline in episodic memory in healthy older adults with high amyloid-beta. J Alzheimers Dis. 2013;33(3):675-9. doi: 10.3233/JAD-2012-121516.

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• Rosario ER, Carroll JC, Pike CJ. Evaluation of the effects of testosterone and luteinizing hormone on regulation of beta-amyloid in male 3xTg-AD mice. Brain Res. 2012 Jul 23;1466:137-45. doi: 10.1016/j.brainres.2012.05.011. Epub 2012 May 14.

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• Cherrier MM, Aubin S, Higano CS. Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer. Psychooncology. 2009 Mar;18(3):237-47. doi: 10.1002/pon.1401.

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  PMID: 27737437 BACKGROUND

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  PMID: 25964245 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Evanthia Galanis, MD

  Alliance Foundation Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: April 6, 2020
• Study Start: August 17, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-04

Locations

US (8)