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

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