Neoadjuvant And Adjuvant Abiraterone Acetate + Apalutamide Prostate Cancer Undergoing Prostatectomy

Inclusion Criteria:

1. Male ≥ 18 years of age.
2. Histologically confirmed adenocarcinoma of the prostate without histological variants comprising \>50% of the sample as determined by academic center central review (including neuroendocrine differentiation, small cell, sarcomatoid, ductal adenocarcinoma, squamous or transitional cell carcinoma).
3. Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within seven months from screening. Less than 3 core biopsies are allowed if the patient has \>1 cm or T3 disease on MRI.
4. Patients must have the following features:

   * Gleason ≥ 4+3=7 OR
   * Gleason 3+4=7 AND at least one of the following: PSA \>20 ng/dL or T3 disease (as determined by MRI).
5. No evidence of metastatic disease as determined by radionuclide bone scans and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
6. Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
8. Participants must have normal organ and marrow function as defined below:

   * Hemoglobin ≥ 9.0 g/dL
   * Absolute neutrophil count (ANC) ≥ 1,500/mcL
   * Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start
   * Serum potassium ≥ 3.5 mmol/L
   * Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin \> 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), alanine aminotransferase (ALT) ≤ 2.5 x ULN
   * Serum albumin ≥ 3.0 g/dL
   * Serum creatinine \< 2.0 x ULN
   * PTT≤60
9. Participant must agree to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or must agree 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. Participant must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
10. Medications known to lower the seizure threshold (see list under APPENDIX D: Representative Medications that May Predispose to Seizure) must be discontinued or substituted at least 1 week prior to study treatment.

Exclusion Criteria:

1. Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, Apalutamide and others), CYP17 inhibitors (including abiraterone acetate, TAK-700, galeterone, ketoconazole, and others), estrogens, Luteinizing Hormone Releasing Hormone (LHRH) agonist/antagonists. Prior therapy with 5α-reductase inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1.
2. Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
3. Prior systemic treatment with an azole drug within two weeks of start of treatment.
4. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone \< 200 ng/dL.
5. Clinically significant cardiovascular disease within 6 months of study treatment including:

   * Severe or unstable angina;
   * Myocardial infarction;
   * Symptomatic congestive heart failure;
   * New York Heart Association (NYHA) class II-IV heart disease;
   * Arterial or venous thromboembolic events (such as pulmonary embolism cerebrovascular accident including transient ischemic attacks);
   * 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 screening EKG \> 470 msec;
   * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
   * Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.
6. History of seizure or any condition or concurrent medication that may predispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Apalutamide, abiraterone acetate, or other study drugs.
8. Severe hepatic impairment (Child-Pugh Class C).
9. Active infection (such as human immunodeficiency virus (HIV) or viral hepatitis) or other medical condition that would make prednisone / prednisolone corticosteroid use contraindicated.
10. History of pituitary or adrenal dysfunction.
11. Gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
12. Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular, or inhaled corticosteroids are permitted.
13. Concomitant use of medications that may alter pharmacokinetics of abiraterone acetate or Apalutamide.
14. Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.
15. Major surgery or radiation therapy within 30 days of screening visit. Participants who have had a major surgery within 30 days of screening visit may be eligible provided the treating investigator deems that the participant is at low risk for complications.
16. Any condition that in the opinion of the investigator would preclude participation in this study.