PHASE 3 STUDY OF DAROLUTAMIDE IN ADDITION TO ADT VERSUS PLACEBO PLUS ADT IN MEN WITH MHSPC

INTERVENTION: Group name:Darolutamide + ADT Type of group;1 N° of participants:370 Intervention(s) description:Darolutamide (BAY 1841788) ; 2 tablets of study drug orally twice daily at approximately 12 hour intervals Additionally the patients will receive ADT of investigator’s choice (LHRH agonist/antagonists or orchiectomy) Group name:Placebo + ADT Type of group;2 N° of participants:185 Intervention(s) description:Placebo matching darolutamide; 2 tablets of study drug orally twice daily at approximately 12 hour intervals Additionally the patients will receive ADT of investigator’s choice (LHRH agonist/antagonists or orchiectomy) CONDITION: ‐C61 Malignant neoplasm of prostate ; Malignant neoplasm of prostate C61 Malignant neoplasm of prostate PRIMARY OUTCOME: ; Outcome name:conventional imaging methods 99mTc‐bone scan for bone metastases criteria and CT/MRI for soft tissue/visceral metastases; Measure:•Radiological progression‐free survival (rPFS) assessed by central review based on RECIST v. 1.1 criteria for soft tissue metastases and PCWG3 criteria for bone metastases; Timepoints:every 12 weeks; SECONDARY OUTCOME: ; Outcome name:Brief Pain Inventory‐Short Form ; Measure:Time to pain progression (Brief Pain Inventory‐Short Form) ; Timepoints:every 12 weeks ; ; Outcome name:Clinic interviews ; Measure:Adverse event assessments using National Cancer Institute–Common Terminology Criteria for Adverse Events (v.5.0) ; Timepoints:every 12 weeks ; ; Outcome name:Clinic interviews ; Measure:Time to initiation of subsequent antineoplastic therapy ; Timepoints:every 12 weeks ; ; Outcome name:Clinic interviews / Review medical history ; Measure:Overall survival – key secondary endpoint ; Timepoints:every 12 weeks ; ; Outcome name:PSA values obtained by central laboratory ; Measure:Prostate‐specific antigen undetectable rates (<0.2 ng/mL) ; Timepoints:every 12 weeks ; ; Outcome name:PSA values obtained by central laboratory ; Measure:Time to Castration‐resistant prostate cancer ; Timepoints:every 12 weeks ; ; Outcome name:PSA values obtained by central laboratory ; Measure:Time to Prostate‐specific antigen progression ; Timepoints:every 12 weeks ; INCLUSION CRITERIA: ‐ Histologically or cytologically confirmed adenocarcinoma of prostate. ‐ Documented metastatic disease by conventional imaging method either by a positive 99mTc‐phosphonate bone scan, or soft tissue or visceral metastases, either by contrastenhanced abdominal/pelvic/chest CT or MRI scan assessed by central review. Note: Metastatic disease is defined as either malignant lesions in bone scan or measurable lymph nodes above the aortic bifurcation or soft tissue/visceral lesions according to RECIST version 1.1. Lymph nodes are measurable if the short axis diameter is ≥15 mm, soft tissue/visceral lesions are measurable if the long axis diameter is ≥ 10 mm. Regional lymph node metastases only (N1, below the aor