Sipuleucel-T With or Without Tasquinimod in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Inclusion Criteria:

* Metastatic asymptomatic or minimally symptomatic castration-resistant prostate cancer (CRPC) patients who are eligible for sipuleucel-T
* Disease progression by PSA criteria (PSA Working Group Consensus Criteria Eligibility) and/or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
* Life expectancy \>= 6 months
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Hemoglobin \>= 100 g/L (\>= 10 g/dL)
* Leukocytes \>= 3,000/mm\^3
* Absolute neutrophil count \>= 1,500/mm\^3
* Platelets \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 x laboratory upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x laboratory upper limit of normal
* Creatinine =\< 1.5 x laboratory upper limit of normal or calculated creatinine clearance of \>= 50 mL/min (please use institutional formula)
* Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5
* Urine protein \< 1+; if \>= 1+, 24 hour urine protein should be obtained and should be \< 1000 mg
* Central nervous system (CNS): no recent history (within 6 month) of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases
* Ability to understand and the willingness to sign a written informed consent document
* Patient verbalizes the ability to swallow and retain oral medication
* Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* Patients who have received systemic steroids within 4 weeks prior to starting study treatment
* Patients who have received prior immunotherapies
* History of therapy for an autoimmune disorder
* Patients receiving any other investigational agents
* Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Association class II, III, or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (less than the last 6 months), cardiac arrhythmia, history of cerebrovascular accident (CVA) within 6 months; no uncontrolled hypertension (defined as blood pressure of \> 160/90 mmHg) on medication or, history of peripheral vascular disease
* Ongoing treatment with warfarin unless the international normalized ratio (INR) is well controlled and below 4
* History of psychiatric illness or social situations that would limit compliance with study requirements
* History of pancreatitis
* Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible
* Systemic exposure to ketoconazole or other strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) isoenzyme inhibitors or inducers within 14 days prior to the start of study treatment; systemic exposure to aminodarone is not allowed within 1 year prior to the start of study treatment
* Ongoing treatment with sensitive cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment
* Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of therapy
* Unwilling or unable to follow protocol requirements
* Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug