Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide
- Interventional
- Recruiting
- NCT04335682
Contact Information
A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)
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.
The goal of the trial is to assess cognitive and quality of life outcomes over the 52-week
primary data collection period of the trial. This is a prospective, randomized, open-label
phase II study comparing cognitive outcomes between men with metastatic or non-metastatic
CRPC (mCRPC or M0CRPC) treated with darolutamide or enzalutamide. This will be a multicenter
trial conducted at 12 sites across the US.
The primary endpoint will be the percent change in the maximally changed cognitive domain by 24 weeks in each study arm. Patients will be stratified by age (<65, 65-80, > 80). Patients will be allowed to cross over from either treatment to the opposite treatment arm at 12 and 24 weeks if they meet any of the cross-over criteria as described in the protocol.
Cognitive assessments will be performed using Cambridge Neuropsychological Test Automated Battery (CANTAB), an internationally recognized software for assessing cognitive function and impairment. Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
Blood samples will be collected for exploratory genomic analyses (AR CAG repeat length, PHS, exosome analysis).
Patients will have the option to opt into an additional separate MRI sub-study. A subset of 40 patients (20 per arm) will undergo fMRI to measure percent signal change in the HP PFC circuit at baseline, 24 and 52 weeks or/and cross-over/end of treatment visit (if applicable).
The primary endpoint will be the percent change in the maximally changed cognitive domain by 24 weeks in each study arm. Patients will be stratified by age (<65, 65-80, > 80). Patients will be allowed to cross over from either treatment to the opposite treatment arm at 12 and 24 weeks if they meet any of the cross-over criteria as described in the protocol.
Cognitive assessments will be performed using Cambridge Neuropsychological Test Automated Battery (CANTAB), an internationally recognized software for assessing cognitive function and impairment. Tests available in the CANTAB battery include tests of learning and executive function; working memory; visual, verbal and episodic memory; and attention, information and processing time. The maximally changed cognitive domain is defined as the domain most changed from baseline in each individual.
Blood samples will be collected for exploratory genomic analyses (AR CAG repeat length, PHS, exosome analysis).
Patients will have the option to opt into an additional separate MRI sub-study. A subset of 40 patients (20 per arm) will undergo fMRI to measure percent signal change in the HP PFC circuit at baseline, 24 and 52 weeks or/and cross-over/end of treatment visit (if applicable).
Gender
Male
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
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 stabilized.
- 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).
- 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 stabilized.
- 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).