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

Trial Status: Active

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.

Inclusion Criteria

  • Have diagnosis of prostate cancer and have received treatment with GnRH agonist or antagonist therapy or orchiectomy for at least 1 month prior to enrollment
  • Several testing instruments employed in this study are only available in English, so enrolled patients must have a command of English that enables them to complete testing without interpretation of questions into other languages. This stipulation is in place because not all of the proposed quality of life or cognitive tests are available or validated in other languages
  • 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), castration-resistant metastatic prostate cancer (mCRPC) OR have non-metastatic castration-resistant prostate cancer (M0CRPC) and eligible to undergo standard of care (SOC) treatment with abiraterone acetate (mHSPC or mCRPC) or enzalutamide (mCRPC, mHSPC, and M0CRPC) * Note: mHSPC patients must have received >= 4 weeks of GnRH agonist or antagonists or orchiectomy prior to starting abiraterone or enzalutamide
  • 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 =< 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; patient must have only grade 2 or less adverse effects from definitive radiation therapy or surgery at the time of registration; radiation of any duration during study follow up is permitted
  • Patients must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must be able to undergo brain MRI (patients must not have any contraindications to MRI imaging). * Note: MRI should be completed before initiating AR-directed therapy if possible, or within 7 days after starting AR-directed therapy
  • 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 (treatment for =< 14 days prior to completing baseline tests is acceptable)
  • 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
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or abiraterone acetate are not eligible

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: David VanderWeele
Phone: 312-926-2413

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: ACTIVE
Contact: Charles Ryan
Phone: 612-625-1110
Email: ryanc@umn.edu

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE
Contact: Kelvin A. Moses
Phone: 615-343-1317

PRIMARY OBJECTIVE:

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.

CORRELATIVE 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 Phase NA

Trial Type Supportive care

Lead Organization
Northwestern University

Principal Investigator
David VanderWeele

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