Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
• Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
• Prostate-specific Antigen (PSA) doubling time of ≤ 10 months and PSA > 2ng/ml.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Blood counts at screening: haemoglobin ≥ 9.0 g/dl,absolute neutrophil count ≥ 1500/µl, platelet count ≥ 100,000/µl.
• Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤ 2.0 x ULN.
• Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.

Exclusion Criteria

• History of metastatic disease at any time or presence of detectable metastases.
• Acute toxicities of prior treatments and procedures not resolved to grade ≤ 1 or baseline before randomisation.
• Prior treatment with: second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor.
• Use of estrogens or 5-α reductase inhibitors or AR inhibitors.
• Prior chemotherapy or immunotherapy for prostate cancer.
• Use of systemic corticosteroid.
• Radiation therapy within 12 weeks before randomisation.
• Severe or uncontrolled concurrent disease, infection or co-morbidity.
• Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
• Known hypersensitivity to the study treatment or any of its ingredients.
• Major surgery within 28 days before randomisation.
• Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
• Uncontrolled hypertension.
• Prior malignancy.
• Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
• Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
• Treatment with any investigational drug within 28 days before randomisation.
• Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures.