Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer

Inclusion Criteria

• Adenocarcinoma of the prostate with histological or cytological confirmation without neuroendocrine differentiation or small cell histology and with G 4+3 or higher, and PSA ≥ 10, and ≥T2b, for whom radical prostatectomy has been recommended and who choose to undergo radical prostatectomy.
• A minimum tissue requirement of ≥3 core biopsies with tumor involvement and at least 50% tumor involvement in one of the core biopsies is required.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Hemoglobin of ≥ 10 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
• Platelet count of ≥ 100k/mL independent of transfusion and/or growth factors within 3 months prior to randomization
• Serum albumin ≥3.0 g/dL
• Serum creatinine 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
• Be capable of swallowing study agents whole as a tablet
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study.
• 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 following the last dose of study drug.

Exclusion Criteria

• The use of any prior hormones including luteinizing hormone-releasing hormone (LHRH) agonists , LHRH antagonists, antiandrogens such as bicalutamide, flutamide and nilutamide, and/or the use of 5-alpha reductase inhibitors, prostate cancer (PC) Spes (or PC-x product), Megestrol Acetate, or estrogen containing nutriceuticals within 6 months of study treatment initiation.
• Prior radiation therapy, immunotherapy, chemotherapy or other investigational therapy given for prostate cancer.
• "Currently active" second malignancy other than non-melanoma skin cancers or non-muscle invasive transitional cell carcinoma of bladder. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse.
• History of seizure or 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 randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
• Current systemic steroid therapy (inhaled or topical steroids are also not allowed)
• Have received treatment with any form of therapy with CYP17 inhibitory activity such as ketoconazole, aminoglutethimide, or an antiandrogen such as bicalutamide within 6 months of study treatment initiation.
• Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids within 6 months of enrollment
• Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
• Have uncontrolled hypertension;subjects with a history of hypertension are permitted in the study provided their blood pressure is controlled by anti-hypertensive therapy, at the discretion of the treating physician
• Have a known history of pituitary or adrenal dysfunction
• Have clinically significant heart disease as evidenced by severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembol