Cognitive Effects of Androgen Receptor Directed Therapies for Advanced Prostate Cancer

NCT03016741 | Active Not Recruiting Phase 4 DMC FDA Drug

• 3 other identifiers: NU 17U19STU00206082NCI-2016-01795
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial studies cognitive function in men with prostate cancer treated with androgen receptor directed therapies such as abiraterone acetate and enzalutamide. The investigators use MRI imaging (non-invasive, non-contrast) to see whether there are changes in brain structure or activity related to treatment that may be related to changes in cognitive function. The investigators are also looking for genetic variations that might make patients more or less sensitive to cognitive changes during treatment for prostate cancer.

Conditions

Castration-Resistant Prostatic Cancer; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer; Hormone-Refractory Prostate Cancer

Keywords

cognitive function; hormonal therapy; cancer survivorship; dementia; cognitive dysfunction; mild cognitive impairment

Outcome Measures

Primary Outcomes (1)

• Cognitive function defined by overall Cogstate score and Cogstate module scores for each domain

  Raw scores on each module of the Cogstate test will be converted to standardized scores (z-scores and T-scores) according to age and/or education-adjusted published normative data per the Cogstate protocol. Linear regressions will be utilized to assess the mean differences between groups at each time point after the baseline while adjusting for baseline scores.

  Measured at baseline, 3 months, 6 months, and 12 months

Secondary Outcomes (5)

• Quality of life assessed using European Organization for Research and Treatment of Cancer quality of life questionnaire-C30 (EORTC QLQ C-30)

  Measured at baseline, 3 months, 6 months, and 12 months

• Fatigue assessed using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT- Fatigue)

  Measured at baseline, 3 months, 6 months, and 12 months

• Subjective measure of cognitive function by FACT-Cog

  Measured at baseline, 3 months, 6 months, and 12 months

• Depression by Patient Health Questionnaire (PHQ-9)

  Measured at baseline, 3 months, 6 months, and 12 months

• Instrumental activities of daily living by Texas Functional Living Scale

  Measured at baseline, 3 months, 6 months, and 12 months

Other Outcomes (2)

• SNPs associated with cognitive function

  SNP chip assessment using blood drawn at baseline or 3 month visit

• Imaging assessed by MRI

  Baseline and 3 months

Study Arms (2)

Arm I (abiraterone acetate, prednisone)

OTHER

Patients receive standard of care treatment with GnRH agonist/antagonist therapy. Patients also receive abiraterone acetate PO and prednisone PO BID in the absence of disease progression or unacceptable toxicity. Patients then undergo cognitive assessment comprising of neuro-cognitive tests and assessments of overall quality of life, fatigue, pain, and symptoms at baseline, 3, 6, and 12 months. Patients also undergo MRI program for 40 minutes comprising of DTI, fMRI, ASL MRI, MPRAGE MRI, FLAIR MRI, and BOLD MRI at baseline and 3 months.

Biological: GnRH agonist/antagonist; Drug: Prednisone; Drug: Abiraterone Acetate

Arm II (enzalutamide)

OTHER

Patients receive standard of care treatment with GnRH agonist/antagonist therapy. Patients also receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo cognitive assessment and MRI program as in Arm I.

Biological: GnRH agonist/antagonist; Drug: Enzalutamide

Interventions

Prednisone DRUG

Given by mouth

Arm I (abiraterone acetate, prednisone)

Abiraterone Acetate DRUG

Given by mouth

Also known as: Zytiga

Arm I (abiraterone acetate, prednisone)

Enzalutamide DRUG

Given by mouth

Also known as: Xtandi

Arm II (enzalutamide)

GnRH agonist/antagonist BIOLOGICAL

Given GnRH agonist/antagonist therapy

Arm I (abiraterone acetate, prednisone); Arm II (enzalutamide)

Eligibility Criteria

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

You may qualify if:

• Have diagnosis of prostate cancer and have received treatment with GnRH agonist or antagonist therapy for at least 1 month prior to enrollment.
• Willing and able to complete survey questionnaires in English without assistance through the duration of the study. This stipulation is in place because not all of the proposed quality of life or cognitive tests are available or validated in other languages.
• Age ≥ 18 years.
• Ability to understand and the willingness to sign a written informed consent document written in English that is approved by an institutional review board.
• Have either newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) or castration-resistant metastatic prostate cancer (mCRPC) and eligible to undergo treatment with abiraterone acetate (mHSPC or mCRPC) or enzalutamide (mCRPC)
• Patients may have received the following prior AR directed therapy prior to enrollment: bicalutamide, ketoconazole. Prior to enrollment, patients may have received treatment with abiraterone acetate or enzalutamide for no more than 14 days before completing baseline studies.
• Patients may have received chemotherapy for hormone-sensitive metastatic prostate cancer only, but it must not have lasted for more than 6 months. At least 12 months must have elapsed since completion of chemotherapy.
• Patients may have received prior definitive radiation therapy or surgery. At least 60 days must have elapsed since completion of definitive radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration. Enrollment during palliative radiation of ≤ 10 days, or radiation of ≤ 10 days during the duration of the study is allowed.
• Patients must be able to take oral medication.

You may not qualify if:

• Prior treatment with enzalutamide or abiraterone acetate for \> 14 days prior to enrollment and completion of baseline tests.
• Receipt of chemotherapy for prostate or other cancer within the past 12 months with residual cognitive deficits, or receipt of chemotherapy for mCRPC. Patients/physicians planning treatment with chemotherapy during the 12 month period of the investigation are also ineligible.
• History of cognitive impairment or dysfunction, including a history of dementia, Alzheimer's disease, stroke with residual cognitive deficits, cognitive dysfunction related to alcohol or substance abuse, or cognitive dysfunction related to prior treatment for any cancer.
• Patients with a seizure history, history of recurrent falls, or known brain metastases are excluded from this clinical trial because of their poor prognosis and because of their heightened risk of seizure or progressive cognitive and/or neurologic dysfunction that would confound the evaluation.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year. Patients with cognitive dysfunction related to treatment of another malignancy, including a history of "chemo-brain", are ineligible.
• Patients taking psychotropic medications or illicit drugs that may alter cognition, concentration, or behavior. Appropriate treatment by a licensed provider with medications for depression or anxiety, including but not limited to SSRIs, SNRIs, and standard dose benzodiazepines at a stable dose, is permitted

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (5)

City of Hope Comprehensive Cancer Center

Los Angeles, California, 91010, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112, United States

Location

University of Minnesota: Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms; Dementia; Cognitive Dysfunction

Interventions

Gonadotropin-Releasing Hormone; Prednisone; Abiraterone Acetate; 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; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstenes; Androstanes

Study Officials

• David VanderWeele, M.D., M.P.H.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: January 11, 2017
• Study Start: March 31, 2017
• Primary Completion: January 4, 2023
• Study Completion (Estimated): August 1, 2029
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

US (5)