Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer

Prior treatment

• Severe untreated infection that in the opinion of the investigator would interfere with participant safety or compliance on trial within 28 days prior to enrollment
• Use of systemic therapy for the treatment of prostate adenocarcinoma within 2 weeks of initiating study treatment

Other illness

• Any condition that would prohibit the understanding or rendering of informed consent
• A history of any other active malignancy with progression and requiring treatment/intervention, with the exception of cutaneous malignancies such as basal cell carcinoma, squamous cell carcinoma, melanoma, or the type of malignancy being studied in this protocol

Lab values

• Any condition, including concomitant disease, additional malignancies, laboratory abnormalities, or psychiatric illness, that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial

Other

• Participants with urinary outflow obstruction that has not been treated or managed with either indwelling catheter or self-catheterization

• Ability to understand and willingness to sign an informed consent form
• Ability to adhere to the study visit schedule and other protocol requirements
• Adults \>= 18 years of age at time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
• Life expectancy \>= 3 months
• Histologically or cytologically confirmed prostate adenocarcinoma
• Metastatic status defined as at least 1 documented metastatic lesion on a bone scan, a computed tomography (computed tomography \[CT\] or CT/ positron emission tomography \[PET\]) scan, or a magnetic resonance imaging (MRI) scan
• Must have less than 50 ng/dL testosterone
• Must have demonstrated disease progression after treatment with 2 or more prior lines of therapies for castration resistant prostate cancer (CRPC), including one second generation androgen targeted agent (such as abiraterone or enzalutamide).
• PSA defined progression after most recent directed therapy. Progression is defined as PSA increase \>= 25% of baseline or absolute increase of \>= 2 ug/L on two PSA measurements at least 7 days apart
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 8 g/dL
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) levels =\< 2.5 × ULN or AST and ALT levels =\< 5 x ULN (for participants with documented metastatic disease to the liver)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (for participants on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment)
• Creatinine clearance \> 30 mL/min by Cockcroft-Gault formula
• Participants with BRCA1/2 or homologous recombination (HR) deoxyribonucleic acid (DNA) repair mutations, and/ or microsatellite instability (MSI) must have received prior treatment (e.g., PARP \[poly adenosine diphosphate-ribose polymerase\] inhibitors or other agents) for BReast CAncer gene (BRCA)/ homologous recombination (HR) DNA repair mutation and/ or MSI
• Participants with known active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \< 100 IU/mL prior to first dose of trial treatment. Participants with treated or untreated hepatitis C virus (HCV) are allowed.
• Male participants who agree to use highly effective method of birth control with their partner (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices \[IUDs\], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug