A phase II, randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist versus anti-androgen therapy (AAT) with apalutamide in patients with biochemical progression after radical prostatectomy

Prior treatment

• 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 randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
• History of any of the following: 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 randomization
• Patients already included in another clinical trial involving an experimental drug.

Other illness

• Allergies, hypersensitivity or known intolerance to the study drugs or excipients.
• Current evidence of uncontrolled hypertension or gastrointestinal disorder affecting absorption

Other

• Patients with severe erectile dysfunction according to international index of erectile function (IIEF-5) questionnaire (score 1-7)

• Male, > 18 years old
• Serum albumin ≥3.0 g/dL
• Serum creatinine <2.0 × upper limit of normal
• Serum potassium ≥3.5 mmol/L
• Serum total bilirubin ≤1.5 × ULN (note: in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
• Patient 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.
• Patients who have received the information sheet and signed the informed consent form
• Patients must be willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• ECOG 0-1
• Histologically confirmed adenocarcinoma of the prostate
• Previous radical prostatectomy (RP), pT2-3, pN0 or pNx
• PSA detectable with confirmed rise (at least 2 weeks apart) at least 8 weeks after RP
• Hormone-naive disease
• Patients amendable to take oral medication
• Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
• Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization