Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer
Condition: Prostate Cancer Non-Metastatic; Castration-Resistant
MeSH terms: Prostatic Neoplasms
Intervention: Darolutamide (Nubeqa, BAY1841788); Placebo
Intervention description: Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg.; Matching placebo 2 tablets twice daily with food.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1509.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the safety and efficacy of BAY1841788 (ODM-201) in
      patients with non-metastatic castration-resistant prostate cancer.
    

Eligibility criteria:

        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.