Neoadjuvant Degarelix With or Without Apalutamide (ARN-509) Followed by Radical Prostatectomy

PRIMARY OBJECTIVE: To assess the difference in antitumor effect between the treatment arms by measuring MRD following radical prostatectomy.

SECONDARY OBJECTIVES: To measure differences between study arms in

• Proportions of post neoadjuvant prostate specific antigen (PSA) ≤ 0.3 ng/ml as a predictor of prostate cancer mortality
• T down-staging, complete pathological response, PSA kinetics, Testosterone kinetics, operation time, blood loss, grade of surgical difficulty
• New generation hybrid imaging 68Ga PSMA (Prostate-Specific Membrane Antigen) PET/MR (Positron emission tomography/Magnetic Resonance) derived parameters
• Early biochemical recurrence as prognostic factor of prostate cancer mortality
• Transcriptome and genome
• Tissue microarrays (TMA) protein expression (DNA repair, resistance etc.) by immunohistochemistry
• Perioperative safety and tolerability
• Quality of life, erection recovery, continence through validated preoperative and postoperative questionnaires pre and postop (IEEF5, ICIQ, EORTC QLQ-C30)

OUTLINE: interventional, single center, phase II, randomized, double blind, placebo controlled trial.

Inclusion criteria

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
• Male aged 18 years or older (within 80 years)
• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Diagnosis of intermediate (at least 2 of the following factors: cT2b, biopsy GS 7, PSA 10-20ng/ml) or high-risk prostatic adenocarcinoma (clinical stage≥T2c and/or biopsy GS≥8 and/or PSA>20ng/ml), cN0-cN1, cM0.
• Patient amenable for open or robotic radical prostatectomy + pelvic lymph node dissection
• ECOG performance status: 0-1
• Adequate organ function as defined by the following criteria:

• White blood cells (WBC) ≥ 4.0 x109/L
• Platelet count ≥ 100 x109/L
• Hemoglobin ≥9 g/dl
• Creatinine ≤ 2 x ULN
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x upper limit of normality (ULN)
• Total serum bilirubin ≤1.5 x ULN.

Exclusion criteria

• Previous surgical/endoscopic treatments for prostatic disease
• Herbal and non-herbal products that in the opinion of the investigator may decrease PSA levels
• cM1 disease
• Any contraindication for PET or MR investigations
• History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Medications known to lower the seizure threshold
• History of:

• Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer currently in complete remission) within 5 years prior to randomization
• Severe/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 randomization
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥100 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
• Gastrointestinal disorder affecting absorption
• Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures.