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

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Participants with urinary outflow obstruction that has not been treated or managed with either indwelling catheter or self-catheterization
* 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
* 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
* Use of systemic therapy for the treatment of prostate adenocarcinoma within 2 weeks of initiating study treatment