Clinical Trial: Cognitive Effects of Androgen Receptor Directed Therapies for Advanced Prostate Cancer

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Cognitive Effects of Androgen Receptor (AR) Directed Therapies for Advanced Prostate Cancer

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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare cognitive function and associated mediators of cognitive function (quality of life, depression, pain, and fatigue) of men with metastatic castration-resistant prostate cancer (mCRPC) during treatment with enzalutamide and abiraterone acetate.

SECONDARY OBJECTIVES:

I. To identify characteristics of men with mCRPC associated with change in cognitive function during treatment with androgen receptor (AR) directed therapy.

II. To compare quality of life and associated factors, including fatigue, pain, and depression, of men with mCRPC during treatment with enzalutamide and abiraterone acetate.

TERTIARY OBJECTIVES:

I. To analyze whether single nucleotide polymorphisms (SNPs) may be associated with change in cognitive function during treatment with AR directed therapy.

II. To compare the functional and structural components of the brain over time and between the brains of men with mCRPC treated with enzalutamide or abiraterone acetate using diffusion tensor imaging (DTI), functional MRI (fMRI), arterial spin labeling (ASL), and other advanced neuroimaging techniques.

OUTLINE: Treatment patients with metastatic castration-resistant prostate cancer are randomized to 1 of 2 arms. Control patients receiving long term androgen deprivation therapy will be assessed with the same measures as a control arm.

ARM I: Patients receive standard of care treatment with gonadotrophin releasing hormone (GnRH) agonist/antagonist therapy. Patients also receive abiraterone
Sponsor: Vanderbilt-Ingram Cancer Center

Current Primary Outcome: Cognitive function defined by overall Cogstate score and Cogstate module scores for each domain [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Quality of life assessed using European Organization for Research and Treatment of Cancer quality of life questionnaire-C30 (EORTC QLQ C-30) [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]
    The outcome measure for this questionnaire is the score as determined per standard scoring practices in the EORTC QLQ-C30 scoring manual. Mean scores from the EORTC QLQ-C30 survey instrument will be compared between groups at each time point, and changes in score will be assessed over time for each individual. Generalized linear regressions will be performed to estimate the differences between groups at each time point with adjustment for baseline and other covariates. GEE analysis will be used for the longitudinal data. Spearman p correlation coefficients between the standardized cognitive test scores and the mediators will be evaluated. Multivariable linear regressions for each time point will be performed to test the interactions between the group identity and each of the interested sociodemographic and clinical factors while adjusting for baseline and other covariates.
  • Fatigue assessed using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT- Fatigue) [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]
    The outcome measure for this questionnaire is the score as determined per standard scoring practices with the FACIT-Fatigue scoring manual. Mean scores from the FACIT-Fatigue survey instrument will be compared between groups at each time point, and changes in score will be assessed over time for each individual. Generalized linear regressions will be performed to estimate the differences between groups at each time point with adjustment for baseline and other covariates. GEE analysis will be used for the longitudinal data. Spearman p correlation coefficients between the standardized cognitive test scores and the mediators will be evaluated. Multivariable linear regressions for each time point will be performed to test the interactions between the group identity and each of the interested sociodemographic and clinical factors while adjusting for baseline and other covariates
  • Subjective measure of cognitive function by FACT-Cog [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]
    The outcome measure for this questionnaire is the score as determined per standard scoring practices with the FACT-Cog scoring manual. Mean scores from the FACT-Cog survey instrument will be compared between groups at each time point, and changes in score will be assessed over time for each individual. Generalized linear regressions will be performed to estimate the differences between groups at each time point with adjustment for baseline and other covariates. GEE analysis will be used for the longitudinal data. Spearman p correlation coefficients between the standardized cognitive test scores and the mediators will be evaluated. Multivariable linear regressions for each time point will be performed to test the interactions between the group identity and each of the interested sociodemographic and clinical factors while adjusting for baseline and other covariates.
  • Depression by Patient Health Questionnaire (PHQ-9) [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]
    The outcome measure for this questionnaire is the score as determined per standard scoring practices with the PH-Q 9 scoring manual. Mean scores from the PHQ-9 survey instrument will be compared between groups at each time point, and changes in score will be assessed over time for each individual. Generalized linear regressions will be performed to estimate the differences between groups at each time point with adjustment for baseline and other covariates. GEE analysis will be used for the longitudinal data. Spearman p correlation coefficients between the standardized cognitive test scores and the mediators will be evaluated. Multivariable linear regressions for each time point will be performed to test the interactions between the group identity and each of the interested sociodemographic and clinical factors while adjusting for baseline and other covariates.
  • Instrumental activities of daily living by Texas Functional Living Scale [ Time Frame: Measured at baseline, 3 months, 6 months, and 12 months ]
    This measure will provide a score to represent patient's ability to complete daily tasks, and is a "direct assessment" based approach to measure instrumental activities of daily living.


Original Secondary Outcome: Same as current

Information By: Vanderbilt-Ingram Cancer Center

Dates:
Date Received: December 1, 2016
Date Started: January 2017
Date Completion: August 2019
Last Updated: January 6, 2017
Last Verified: January 2017