Table 2.

Summary of ongoing clinical trials evaluating CNS effects of androgen ablation therapy in men with prostate cancer.

NCT number/study name	Study design	Primary objectives	Secondary objectives	Estimated enrollment	Primary completion date	Potential limitations
NCT03016741	Prospective, phase 4, interventional, randomized, parallel assignment study to investigate cognitive function in men with mCRPC treated with abiraterone acetate – or enzalutamide (+ADT)	Cognitive function defined by overall Cogstate score and Cogstate module scores for each domain (measured at baseline, 3, 6, and 12 months)	EORTC QLQ-C30, FACIT- Fatigue, FACT-Cog, depression by PHQ-9, instrumental activities of daily living by Texas Functional Living Scale (measured at baseline, 3, 6, and 12 months), SNPs associated with cognitive function, imaging assessed by MRI	100	August 2020	A well-designed trial that may answer some important questions on cognitive function
NCT03927391/ REDOSE	Prospective, phase 4, randomized, parallel assessment study to investigate reduced enzalutamide dose on cognitive side effects in frail patients with mCRPC	Change in fatigue after 6 weeks of treatment, as measured by FACIT-Fatigue	Decrease in fatigue after 12 and 24 weeks of treatment; cognitive impairment and its impact on QoL (measured by FACT-Cog and MoCA); changes in depression score (measured by GDS-15; all at 6, 12, and 24 weeks)	50	May 2021	A well-designed trial, although sample size is not large. QoL is measured by PRO only; MoCA is not a comprehensive test battery
NCT03016741/ COG-CaP	Prospective, randomized trial comparing cognitive effects of enzalutamide and abiraterone acetate in men with mCRPC	Compare cognitive function and associated mediators in men with mCRPC or mHSPC during treatment with enzalutamide (mCRPC only) or abiraterone acetate (mCRPC or mHSPC)	Identify characteristics associated with change in cognitive function in men with mCRPC, during AR-directed therapy. Compare QoL and associated factors of men with mCRPC during enzalutamide/abiraterone acetate therapy	100	August 2020	Trial is not randomized, and does not appear to include formal neurocognitive testing
NCT02907372/COG-PRO	Prospective, open-label, interventional, diagnostic study on the impact of abiraterone acetate and enzalutamide in elderly patients with mCRPC	The proportion of elderly patients who will experience increased cognitive concerns (at least for one cognitive complaint) by questionnaires (3 months after initiation of treatment)	Questionnaires on cognitive function, QoL, anxiety/depression, fatigue, observance of treatment, and autonomy after 12 months	222	December 2019	This study uses questionnaires (rather than formal neurocognitive testing), obtained at 3 months, not baseline
NCT00579072	Observational case–control study to assess the impact of androgen ablation therapy (leuprolide acetate, bicalutamide, goserelin, or degarelix acetate) on cognitive functioning and functional status in elderly men (aged ≥65 years) with prostate cancer	Describe changes in cognitive functioning over 6 months in men who are about to start androgen ablation therapy vs. men with neuroendocrine differentiation and no medical indication to start comparison androgen ablation therapy (3 years)	Differences in cognitive functioning of patients with comparison androgen ablation therapy vs. those who are hormone naïve or who received androgen ablation therapy, regionally specific differences in brain activity mediated by testosterone, and differences in neuropsychological performance	280	December 2019	This study uses questionnaires (rather than formal neurocognitive testing)
NCT03124615/EFFECT	Phase 2, open-label, interventional study in patients with mCRPC who have started enzalutamide treatment and have grade 3 fatigue and/or cognition complaints to determine whether dose reduction of enzalutamide will lead to an improvement in symptoms while maintaining active drug levels	The proportion of patients who have an improvement in cognition/fatigue symptoms after 12 months	–	47	December 2020	Cognitive function alterations are patient-reported only

ADT androgen deprivation therapy, AR androgen receptor, EORTC QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, FACIT-Fatigue Functional Assessment of Chronic Illness Therapy Fatigue Subscale, FACT-Cog Functional Assessment of Cancer Therapy-Cognitive, GDS geriatric depression scale, HRQoL health-related quality of life, mCRPC metastatic castration-resistant prostate cancer, mHSPC metastatic hormone-sensitive prostate cancer, MoCA Montreal Cognitive Association Montreal Cognitive Association, MRI magnetic resonance imaging, PHQ-9 Patient Health Questionnaire, PRO patient-reported outcome, QoL quality of life, SNP single nucleotide polymorphism