Apalutamide in Treating Patients With Prostate Cancer Who Are in Active Surveillance

This phase II trial studies how well apalutamide works in treating patients with prostate cancer who are in active surveillance. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells.

OUTLINE:

Patients receive apalutamide orally (PO) once daily (QD) for 90 days in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed up at 180, 365, 545, and 730 days; and at years 3, 4 and 5 by medical record review.

Eligibility Criteria:
Inclusion Criteria:

* Have signed an informed consent document
* Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
* Written authorization for use and release of health and research study information has been obtained
* Life expectancy \>= 10 years (as determined by the treating physician)
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
* Histologically confirmed adenocarcinoma of the prostate as documented by a minimum 12 core prostate biopsy completed within 1-year of enrollment (note: most recent prostate biopsy must have demonstrated prostatic adenocarcinoma)
* Favorable risk prostate cancer as defined by:

  * Very low-risk:

    * Clinical stage T1c disease
    * PSA density (PSAD) \< 0.15 ng/mL
    * Gleason score 6
    * =\< 2 core biopsies with =\< 50% involvement of any biopsy core with cancer, or unilateral disease =\< 2 core biopsies with any percentage involvement OR
  * Low risk:

    * Clinical stage =\< T2a
    * PSA \< 15 ng/mL
    * Gleason score 6 OR
  * Low-intermediate risk:

    * Clinical stage T1c
    * PSA \< 15 ng/ml
    * Gleason 3+4 present in =\< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy
    * Gleason 6 disease in all other cores / sites
* Willing and qualified for active surveillance at Johns Hopkins or the University of Washington
* Serum testosterone \>= 150 ng/dL
* Able to swallow the study drugs whole as a tablet
* Hemoglobin \>= 9.0 g/dL, (at screening), independent of transfusion and/or growth factors within 3 months prior to registration
* Platelet count \>= 100,000 x 10\^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to registration
* Serum albumin \>= 3.0 g/dL (at screening)
* Glomerular filtration rate (GFR) \>= 45 mL/min (at screening)
* Serum potassium \>= 3.5 mmol/L (at screening)
* Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) (at screening) (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) or alanine aminotransferase (ALT) \< 2.5 × ULN (at screening)
* Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
* 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

Exclusion Criteria:

* Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
* Prior use of ARN-509 (apalutamide)
* Have known allergies, hypersensitivity, or intolerance to ARN-509 (apalutamide) or its excipients
* Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

  * Hormonal therapy (e.g. leuprolide, goserelin, triptorelin)
  * Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole)
  * Antiandrogens (e.g. bicalutamide, nilutamide)
  * Second generation antiandrogens (e.g. enzalutamide)
  * Immunotherapy (e.g. sipuleucel-T, ipilimumab)
  * Chemotherapy (e.g. docetaxel, cabazitaxel)
* Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
* History of any of the following:

  * Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to registration, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  * Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration
  * Any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:

  * Uncontrolled hypertension
  * Gastrointestinal disorder affecting absorption
  * Active infection (e.g. human immunodeficiency virus \[HIV\] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  * Any condition that in the opinion of the investigator, would preclude participation in this study
* The use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
* The use of strong CYP3A4 inhibitors, including: itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice (or grapefruits)

  * Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide
* Strong CYP3A4 inducers, including: phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, efavirenz, tipranavir, St. John's wort

  \*\*Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide
* Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule