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.