ARACOG: A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated with Darolutamide or Enzalutamide

Protocol # :
Metastatic Prostate Cancer
Prostate Cancer Metastatic
Prostate Cancer
Castrate Resistant Prostate Cancer
Disease Sites
Principal Investigator
Morgans, Alicia, K
Site Research Nurses
Bretta, Katherine, v.
Carey, Margaret, M.
Fleming, Norah, Michelle
Freeman, Stefani, Danielle
Gentile, Alissa
Ginter, Lindsey
Healy, Erin, C.
Hixon, Nicole, R.
Houghton, Nicole
Kabarame, Liliane
Kabarame, Liliane
Katica, Dean
Kosinski, Michelle
Leisner, Claire
Mingrino, Sage
Prisby, Judith

Trial Description

This is a prospective, randomized, open-label phase II study comparing cognitive outcomes
between men with non-metastatic and metastatic castration-resistant prostate cancer (mCRPC or
M0CRPC) treated with darolutamide or enzalutamide. Approximately 132 patients will be
enrolled. Eligible patients will be randomized in a 1:1 fashion to treatment with
enzalutamide 160 mg orally daily or darolutamide 600 mg orally twice daily, in combination
with standard LHRH agonist based treatment. Cognitive assessments will be performed using
modules from Cambridge Neuropsychological Test Automated Battery (CANTAB) an internationally
recognized software for assessing cognitive function and impairment.

Eligibility Requirements

Key inclusion criteria include:

- Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation or small cell features

- Progressive disease per PCWG3 criteria

- Metastatic CRPC or non-metastatic CRPC (M0CRPC)

- Castration-resistant prostate cancer demonstrated during continuous ADT, defined
as 3 PSA rises at least 1 week apart, with the last PSA >2 ng/mL.

- For mCRPC: metastatic disease documented by standard or novel imaging techniques
OR for M0CPRC: no evidence of metastatic disease on standard imaging.

- Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the
patient is medically castrated, continuous dosing with GnRHa must have been initiated
at least 4 weeks prior to randomization and must be continued throughout the study.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Able to complete cognitive testing and patient reported outcome surveys in English.

- Ability to swallow study tablets whole.

- Able to provide informed consent.

Key exclusion criteria include:

- Prior chemotherapy for treatment of CRPC. Patients who received chemotherapy for
castrate-sensitive prostate cancer are still eligible provided chemotherapy was
completed >6 months prior to study entry.

- Use of investigational agents for the treatment of prostate cancer within 4 weeks of
study entry.

- Prior usage of ENZ or DARO.

- Prior use of apalutamide

- Prior use of investigational agents that act on the androgen axis.

- Progression during treatment with abiraterone (PSA or radiographic progression). Must
have < 12 weeks of abiraterone exposure prior to enrollment if given for treatment of
CRPC. If used with radiation for high risk localized hormone sensitive disease, can
enroll if no progression of disease during treatment with abiraterone (PSA or
radiographic) and >6 months since last exposure to abiraterone.

- Planned radiation treatment > 21 days during enrollment in the study.

- Any active, or prior history of, brain metastasis that have not been treated and

- Active or history of seizures or seizure disorder.

- Prior diagnosis of dementia or other neurologic impairment.

- Use of chronic opiates (other than stable doses of opioids that in the view of the
patient and investigator do not affect cognition).

- Clinically significant history of falls or risk of falls at baseline (timed up-and-go
(TUG) test time of >12 seconds).