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

Condition: Castration-Resistant Prostatic Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer, Hormone-Refractory Prostate Cancer


  • Biological: GnRH agonist/antagonist
  • Drug: Prednisone
  • Drug: Abiraterone Acetate
  • Drug: Enzalutamide

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03016741

Sponsor: Vanderbilt-Ingram Cancer Center

Primary Outcome Measures:

  • Measure: 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
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: 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
  • Safety Issue:
  • Measure: Fatigue assessed using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT- Fatigue)
  • Time Frame: Measured at baseline, 3 months, 6 months, and 12 months
  • Safety Issue:
  • Measure: Subjective measure of cognitive function by FACT-Cog
  • Time Frame: Measured at baseline, 3 months, 6 months, and 12 months
  • Safety Issue:
  • Measure: Depression by Patient Health Questionnaire (PHQ-9)
  • Time Frame: Measured at baseline, 3 months, 6 months, and 12 months
  • Safety Issue:
  • Measure: Instrumental activities of daily living by Texas Functional Living Scale
  • Time Frame: Measured at baseline, 3 months, 6 months, and 12 months
  • Safety Issue:

Estimated Enrollment: 100

Study Start Date: March 31, 2017

Phase: Phase 4


  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • Have pathologic diagnosis of prostate cancer and have received treatment with GnRH agonist or antagonist therapy for at least 3 months prior to enrollment
  • Willing and able to complete survey questionnaires in English with or without assistance through the duration of the study
  • Life expectancy >= 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • 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 castration-resistant metastatic disease (mCRPC) defined by the following:
  • Castrate serum testosterone level =< 50 ng/dL (1.7 nmol/L)
  • Bilateral orchiectomy or maintenance on androgen ablation therapy with GnRH agonist or antagonist throughout the study (including the follow-up period)
  • Serum prostate specific antigen (PSA) progression, defined as two consecutive increases in PSA over a previous reference value within 6 months prior to enrollment, with each progression measurement at least 1 week apart
  • Willing and medically able to receive treatment with first-line AR directed therapy with abiraterone acetate or enzalutamide as determined and prescribed by the primary physician
  • Patients may have received the following prior AR directed therapy >= 24 months prior to enrollment: bicalutamide, ketoconazole; prior to enrollment, patients may have received treatment with abiraterone acetate or enzalutamide for no more than 7 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 radiation therapy or surgery; however, at least 60 days must have elapsed since completion of radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration
  • Patients must be able to take oral medication
  • Control patients must be expected to stay on GnRH agonist or antagonist therapy for high-risk localized, biochemical recurrent or hormone-sensitive metastatic prostate cancer for the entire 12 months of the study; examples of eligible patients include long-term androgen deprivation therapy (ADT) use after definitive external beam radiation for high-risk localized prostate cancer, long-term ADT use after prostatectomy for lymph node positive disease, long-term ADT use for biochemical recurrence or elevated PSA post-prostatectomy, or long-term ADT use for hormone sensitive metastatic prostate cancer; control patients should not expect to receive additional treatments for their prostate cancer during the 12 months of the study, including but not limited to additional salvage or adjuvant radiation, surgery, chemotherapy, or other intervention; if these interventions are expected, enrollment should be delayed until after the intervention; unexpected changes in treatment, including the use of medications for mCRPC, are completely acceptable and at the discretion of the treating physician; questions regarding the eligibility of control patients should be directed to the principal investigator (PI)

Exclusion Criteria:

  • Prior treatment with enzalutamide or abiraterone acetate for > 7 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 selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and standard dose benzodiazepines at a stable dose, is permitted
  • Control patients cannot have a diagnosis of mCRPC


  • VICC Clinical Trials Information Program
  • 800-811-8480


  • Vanderbilt-Ingram Cancer Center
  • Nashville Tennessee 37232 United States

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