A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy

Inclusion Criteria:

• Willing and able to provide written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Documented histologically confirmed adenocarcinoma of the prostate
• Willing to undergo prostatectomy as primary treatment for localized prostate cancer
• High risk prostate cancer (per National Comprehensive Cancer Network [NCCN] criteria): Gleason score 8-10 or T3a or PSA > 20 ng/mL or very-high risk prostate cancer (per NCCN criteria): T3b-T4
• Serum testosterone >= 150 ng/dL
• Able to swallow the study drugs whole
• Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing)
• 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
• Medications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry

Exclusion Criteria:

• Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
• Prior use of apalutamide, abiraterone acetate or degarelix

• Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

  • Hormonal therapy (for example [e.g.] leuprolide, goserelin, triptorelin, degarelix)
  • Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)
  • Antiandrogens (e.g. bicalutamide, nilutamide)
  • Second generation antiandrogens (e.g. enzalutamide, apalutamide)
  • Immunotherapy (e.g. sipuleucel-T, ipilimumab)
  • Chemotherapy (e.g. docetaxel, cabazitaxel)
• Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
• Absolute neutrophil count [ANC] < 1500/mm^3
• Platelet count < 100,000/mm^3
• Hemoglobin < 9 g/dL
• Total bilirubin > 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >= 2.5 x ULN; 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
• Abnormal kidney function (glomerular filtration rate GFR < 45 mL/min)
• Serum albumin < 3 g/dL
• Serum potassium < 3.5 mmol/L
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• History of stroke within the last 5-years
• History of gastrointestinal (GI) bleed requiring transfusion
• History of peptic ulcer disease requiring treatment within the last 5-years
• History of asthma that is nonsteroidal anti-inflammatory drug (NSAID)-induced or with asthma that is classified as 'mild-persistent' or worse (based on symptoms occurring more than 2 days per week)
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption
• Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/ prednisolone once daily
• Any condition that in the opinion of the investigator, would preclude participation in this study
• Child Pugh class B & C
• Pre-existing viral hepatitis