Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC

Patients will firstly receive 6 months of darolutamide in combination with docetaxel and ADT treatment.

• When the patient reaches:

• PSA ≤ 0.2ng/ml
• Or PSA > 0.2ng/ml but with more that 90% decrease comparing baseline
• Without newly discovered metastatic lesions. They will be randomly assigned in a 1:1 ratio to either continuous treatment group or intermittent treatment group (1) Continuous treatment group: Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC; (2) Intermittent treatment group: Only ADT as background treatment without Darolutamide. PSA check every three months, when the patient's PSA > 1ng/ml (or PSA > 1ng/ml and PSA has risen by more than 20% comparing baseline), restart the darolutamide, until mCRPC.

• When the patient:

• PSA > 0.2ng/ml and has not decreased by 90% compared to baseline
• Or has new metastatic lesions, they will exit the study. Imaging assessment will be conducted every 3 months

Inclusion criteria

Patients must meet all of the following criteria to be eligible for this study:

• Male aged ≥18 years;
• Histologically or cytologically confirmed prostate adenocarcinoma;
• Metastatic disease (confirmed by conventional imaging);
• ECOG performance status of 0-1;
• Suitable for ADT and docetaxel treatment;
• Good bone marrow, kidney, and liver function:

• (1) Hematological examination (no blood transfusion or use of hematopoietic growth factors within 7 days before screening):

• Hemoglobin (HB) ≥ 90g/L; 2. Absolute neutrophil count (ANC) ≥ 1.5×109/L; 3. Platelets (PLT) ≥ 80×109/L; 2. (2) Blood biochemistry examination (no blood transfusion or albumin within 7 days before screening):

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Total bilirubin (TBIL) ≤ 2.0 × ULN;
• Serum creatinine (Cr) ≤ 2.0×ULN;

• Willing to participate in this study, sign an informed consent form, and have good compliance

Exclusion criteria

• No metastatic disease;
• Prior treatment with: a) Second-generation ARis or other experimental ARis b) CYP17 enzyme inhibitors such as abiraterone acetate or oral ketoconazole for anti-tumor treatment of prostate cancer c) Chemotherapy or immunotherapy prior to randomization for prostate cancer
• Received radiotherapy within 2 weeks before starting 6 months of darolutamide + docetaxel + ADT treatment;
• Stroke, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass surgery, congestive heart failure (New York Heart Association class III or IV);
• History of malignant tumors;
• Planned receipt of other anti-tumor treatment during the study treatment period;
• Known allergy to the above drug components;
• Difficulty swallowing, chronic diarrhea, intestinal obstruction, and various factors affecting drug intake and absorption;
• Refusal to sign the informed consent form;
• Investigator's opinion that the participant is not suitable for inclusion.