A Phase II Study Comparing Salvage Radiotherapy in Combination With 6 Months of Androgen-deprivation Therapy Versus Anti-androgen Therapy With Apalutamide in Patients With Biochemical Progression After Radical Prostatectomy
This is 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 (arm A) versus anti-androgen therapy (AAT) with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm) or 6 28-day cycles of apalutamide 240mg daily (interventional arm). The study will include a screening phase, treatment phase, and a post-treatment phase. The primary objective of the trial is to compare sexual function between the 2 groups based on the Expanded Prostate cancer Index Composite (EPIC)-26 sexual domain scores at 9 months after start of hormonal treatment.
• Male, \> 18 years old.
• 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.
• Patients must have clinical laboratory values at screening:
∙ 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
‣ Serum albumin ≥3.0 g/dL
‣ Serum creatinine \<2.0 × upper limit of normal (ULN)
‣ 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.