A Trial Comparing Docetaxel 75 mg/m2 (3w) Versus Docetaxel 50 mg/m2 (2w) in Combination With Darolutamide + ADT in mHSPC Patients

Prior treatment

• Prior treatment with:
• LHRH agonist/antagonists started more than 12 weeks before randomization Second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, other investigational AR inhibitors
• Chemotherapy, immunotherapy, radium or other therapeutic radiopharmaceuticals for prostate cancer (e.g. Lutetium177-PSMA) prior to randomization
• Treatment with radiotherapy (external beam radiation therapy, brachytherapy) within 2 weeks before randomization
• Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris,coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
• Previous (within 28 days before the start of study drug or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s)
• Inability to swallow oral medications
• Previous assignment to treatment in this study

Other illness

• Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
• Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg despite medical management
• A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study drug
• An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need for treatment
• Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results

Age

• Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed ≥5 years before randomization and from which the subject has been disease-free

Other

• Exclusion criteria
• Contraindication to both CT and MRI contrast agent

• Written informed consent
• Males ≥18 years of age
• Histologically or cytologically confirmed adenocarcinoma of prostate
• Investigator assessed metastatic disease documented either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast-enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan assessed. Metastatic disease is defined as either malignant lesions in bone scan or soft tissue/visceral lesions according to Response Evaluation Criteria In Solid Tumors (RECIST) 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.
• Subjects with lymph node metastases only (either below the aortic bifurcation (N1) or above the aortic bifurcation (M1a)) will not be eligible for the study.
• Subjects must be candidates for ADT, docetaxel and darolutamide therapy per Investigator's judgment
• Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but no longer than 12 weeks before randomization. For subjects receiving LHRH agonists, treatment in combination with a first generation anti-androgen for at least 4 weeks, prior to randomization is recommended. First generation anti-androgen has to be stopped prior to randomization.
• An Eastern Cooperative Oncology Group performance status of 0 or 1
• Blood counts at Screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5x109/L, platelet count ≥100x109/L (subject must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at Screening)
• Screening values of serum alanine aminotransferase and/or aspartate transaminase ≤1.5x upper limit of normal (ULN), total bilirubin ≤ULN, creatinine ≤2.0x ULN
  • Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 3 months after the end of the treatment with darolutamide and 6 months after treatment with docetaxel.