Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

PRIMARY OBJECTIVES: I. To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (\</\>= 50% decline) at 12 weeks versus (vs.) baseline. SECONDARY OBJECTIVES: I. To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause). II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression. III. To identify molecular features and cellular pathways present in tumors from men with metastatic castrate-resistant prostate cancer (CRPC) that are progressing despite enzalutamide treatment. IV. To explore correlation between baseline molecular features and pathways and objective response. V. To assess the correlations between the baseline molecular features and pathways and degree of PSA decline at 12 weeks and maximal PSA decline observed while on study. VI. To assess the correlations between the baseline molecular features and time on treatment. TERTIARY OBJECTIVES: I. To assess correlations between cell-free deoxyribonucleic acid (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples. II. To assess correlations between cfDNA molecular features and endpoints in the primary and secondary objectives listed above. III. To explore correlations with baseline molecular features and tissue histology. IV. To explore correlations with baseline tissue histology and PSA change, time to PSA progression, time on treatment, progression-free survival, and overall survival. OUTLINE: Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide, and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing. After completion of study, patients are followed up every 12 weeks.