Prostate Cancer Clinical Trials

• History of histologically diagnosed prostatic adenocarcinoma

• Participants must have progressed on no more than one novel hormonal therapy (NHT) by PSA or radiographic criteria (per Prostate Cancer Working Group 3 \[PCWG3\] or Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1) and a castrate serum testosterone level (i.e., ≤ 50 ng/dL). If progressive disease by radiographic criteria, PSA must be ≥ 2ng/ml. PSA progression will be defined as at least two successive PSA rises above the nadir, separated by ≥ 1 week, with the last determination having a value of ≥ 2 ng/mL. NHTs include but are not limited to either abiraterone, enzalutamide, darolutamide, or apalutamide. (Biosimilar or generic agents may be allowed at the discretion of the principal investigator \[PI\].) Note: prior NHT exposure that did not result in disease progression will not be counted as prior line, i.e., patient's that completed prior abiraterone course in the localized setting, patients that changed NHT due to toxicity or financial toxicity

• Participants must have previously progressed on a novel hormonal therapy (NHT) by PSA or radiographic criteria (per PCWG3 or RECIST v1.1). NHTs include but are not limited to either abiraterone, enzalutamide, darolutamide, or apalutamide. (Biosimilar or generic agents may be allowed at the discretion of the principal investigator \[PI\].) Note: prior NHT exposure that did not result in disease progression will not be counted as prior line, i.e., patient's that completed prior abiraterone course in the localized setting, patients that changed NHT due to toxicity or financial toxicity

• Participants may have received one prior line of taxane chemotherapy in any setting

• Participants must be \>= 18 years of age prior to signing informed consent

• Eastern Cooperative Oncology Group (ECOG) performance status score =\< 2

• Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization

• Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization

• Absolute neutrophil count \>= 1.5 x 10\^3/mL

• Serum albumin \>= 3.0 g/dL

• Serum creatinine =\< 1.5 mg/dL

• Serum potassium \>= 3.5 mmol/L

• Serum total bilirubin \< 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject may be eligible)

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase =\< 1.5 x ULN

• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

• Medications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry

• Have had no known recent close contact with a person with active tuberculosis (TB) or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation

• Participants must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study