Apalutamide, Abiraterone Acetate, and Prednisone in Treating Participants With Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Presence of metastatic disease that can be biopsied by any methodology applicable
* Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
* Serum testosterone level =\< 50 ng/dL at the screening visit
* Progressive disease defined as one or more of the following three criteria (NOTE: Patients who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen):

  * PSA progression defined by a minimum of two rising PSA levels with an interval of \>= 1 weeks between each determination. The PSA value at the screening visit should be \>= 2 ng/mL
  * Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
  * Bone disease progression defined by two or more new lesions on bone scan
* Patients previously treated with chemotherapy must have no more than two prior chemotherapy regimens for the treatment of metastatic prostate cancer
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Serum albumin \>= 3.0 g/dL
* Serum potassium \>= 3.5 mmol/L
* Estimated life expectancy of \>= 6 months
* Able to swallow the study drug and comply with study requirements
* Willing and able to give informed consent
* Tumor specimen obtained prior to treatment initiation by interventional radiology guided biopsy will be interrogated per immunohistochemistry (IHC) and features should be as follows for a patient to be eligible

  * Overexpression of androgen receptor (AR)-C terminal and AR-N terminal and PTEN with lack of ARV7 expression along with and ki67 =\<10%
  * No combined RB loss and p53 mutation and
  * No expression of neuroendocrine markers CD56 and chromogranin (all markers assessed by standardized IHC protocols)
* 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

  * The methods must consist of a condom and the use of another barrier method (such as a diaphragm or cervical/vault caps) with a spermicidal agent. Your female partner can choose to use an intrauterine device or system (intrauterine device \[IUD\] or intrauterine system \[IUS\]) or use birth control pills, injections, or implants instead of a barrier method

Exclusion Criteria:

* Known allergy to the study drugs or any of its components
* Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
* Known metastases to the brain
* Absolute neutrophil count \< 1000/uL at the screening visit
* Platelet count =\< 100,000 x 10\^9/uL at the screening visit
* Hemoglobin \< 9 g/dL at the screening visit at the screening visit
* NOTE: patients may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the screening visit
* Total bilirubin (Tbili) \> 1.5 times the upper limit of normal at the screening visit
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal at the screening visit
* Creatinine (Cr) \> 2 mg/dL at the screening visit
* History of another malignancy within the previous 2 years with \> 30 % probability of relapse other than curatively treated non-melanomatous skin cancer
* Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or biologic therapy within 4 weeks of enrollment (day 1 visit)
* Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of enrollment (day 1 visit)
* Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
* Structurally unstable bone lesions suggesting impending fracture
* History of seizure or any condition that may increase the patient's seizure risk. Also, history of loss of consciousness or transient ischemic attack within 12 months of day 1
* Clinically significant cardiovascular disease including:

  * Myocardial infarction within 6 months
  * Uncontrolled angina within 6 months
  * Congestive heart failure New York Heart Association (NYHA) class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months results in a left ventricular ejection fraction that is \>= 45%
  * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  * Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) \> 470 msec
  * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
  * Hypotension (systolic blood pressure \< 86 millimeters of mercury or bradycardia with a heart rate of \< 50 beats per minute on any ECG taken at the screening visit
  * Bradycardia with a heat rate of \< 50 beats per minutes in the screening ECG, unless pharmaceutically induced and reversible
  * Chronically uncontrolled hypertension as indicated by consistently elevated resting blood pressure (systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 105 mmHg) during screening
* Have used or plan to use from 30 days prior to enrollment (day 1 visit) through the end of the study the following medications known to lower the seizure threshold:

  * Aminophylline/theophylline
  * Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone)
  * Bupropion
  * Insulin
  * Lithium
  * Pethidine
  * Phenothiazine antipsychotics (e.g., prochlorperazine \[compazine\], chlorpromazine, mesoridazine, thioridazine)
  * Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
* Prior use of ketoconazloe, enzalutamide, abiraterone or apalutamide or participation in a previous clinical trial of ketoconazloe,enzalutamide, abiraterone or apalutamide unless within the neoadjuvant setting
* Use of an investigational agent within 4 weeks of enrollment (day 1)
* Gastrointestinal disorder affecting absorption (e.g., gastrectomy)
* Major surgery within 4 weeks prior to enrollment (day 1)
* History of significant bleeding disorder unrelated to cancer, including:

  * Diagnosed congenital bleeding disorders (e.g., von Willebrand's' disease)
  * Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  * History of gastrointestinal (GI) bleeding within one year
* Known active or symptomatic viral hepatitis or chronic liver disease
* Known history of pituitary or adrenal dysfunction
* Baseline moderate and severe hepatic impairment (Child Pugh class B \& C)