Cognitive Assessment and MRI Program in Identifying Cognitive Effects of Androgen Receptor Directed Therapies in Patients with Advanced Prostate Cancer

Status: Active

Description

This clinical trial studies how well cognitive assessment and magnetic resonance imaging (MRI) program work in identifying cognitive effects of androgen receptor directed therapies such as abiraterone acetate and enzalutamide in patients with prostate cancer that has spread from where it started to other places in the body. Cognitive assessment and MRI program may help to assess the cognitive function of patients during treatment and identify genetic variations that might make patients more or less sensitive to cognitive changes during treatment for prostate cancer.

Eligibility Criteria

Inclusion Criteria

  • Have 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
  • 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

Exclusion Criteria

  • 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 selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and standard dose benzodiazepines at a stable dose, is permitted

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Tanya Barauskas Dorff
Phone: 626-218-6218
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: In review
Contact: Mitchell Eric Gross
Phone: 323-442-1828

Illinois

Chicago
Northwestern University
Status: Active
Contact: Alicia Katherine Morgans
Phone: 312-695-2381
Email: alicia.morgans@northwestern.edu

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: In review
Contact: Charles Ryan
Phone: 612-625-1110

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Kelvin A. Moses
Email: kelvin.a.moses@vanderbilt.edu

Trial Objectives and Outline

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) or metastatic hormone sensitive prostate cancer during treatment with enzalutamide (mCRPC only) and abiraterone acetate (metastatic hormone sensitive prostate cancer [mHSPC] or mCRPC).

SECONDARY OBJECTIVES:

I. To identify characteristics of men with prostate cancer 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 metastatic prostate cancer 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 metastatic prostate cancer treated with enzalutamide or abiraterone acetate using diffusion tensor imaging (DTI), functional MRI (fMRI), arterial spin labeling (ASL), and other advanced neuroimaging techniques.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care treatment with gonadotrophin releasing hormone (GnRH) agonist/antagonist therapy. Patients also receive abiraterone acetate orally (PO) and prednisone PO twice daily (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, Magnetization Prepared Rapid Gradient Echo (MPRAGE) MRI, Fluid attenuated Inversion Recovery (FLAIR) MRI, and blood oxygenation level-dependent (BOLD) MRI at baseline and 3 months.

ARM II: 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.

ARM III: Patients receive standard of care treatment with GnRH agonist/antagonist therapy and undergo cognitive assessment and MRI program as in Arm I.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Supportive care

Lead Organization

Lead Organization
Northwestern University

Principal Investigator
Alicia Katherine Morgans

Trial IDs

Primary ID NU 17U19
Secondary IDs NCI-2016-01795
Clinicaltrials.gov ID NCT03016741