intermittent darolutamide treatment in the triple therapy of mhspc

Conditions: Metastatic Prostate Cancer; Intermitent Anti-androgen Therapy

Summary: to evaluate the efficacy and safety of intermittent use of darolutamide compared to long-term use in combination with adt and docetaxel in the treatment of mhspc patients.

patients will firstly receive 6 months of darolutamide in combination with docetaxel and adt treatment. 1. when the patient reaches: 1. psa ≤ 0.2ng/ml 2. or psa \> 0.2ng/ml but with more that 90% decrease comparing baseline 3. 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. 2. when the patient: 1. psa \> 0.2ng/ml and has not decreased by 90% compared to baseline 2. or has new metastatic lesions, they will exit the study. imaging assessment will be conducted every 3 months

Eligibility criteria:
inclusion criteria: patients must meet all of the following criteria to be eligible for this study: 1. male aged ≥18 years; 2. histologically or cytologically confirmed prostate adenocarcinoma; 3. metastatic disease (confirmed by conventional imaging); 4. ecog performance status of 0-1; 5. suitable for adt and docetaxel treatment; 6. good bone marrow, kidney, and liver function: 1. (1) hematological examination (no blood transfusion or use of hematopoietic growth factors within 7 days before screening): 1. 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): 1. alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 2.5 × uln 2. total bilirubin (tbil) ≤ 2.0 × uln; 3. serum creatinine (cr) ≤ 2.0×uln; 7. willing to participate in this study, sign an informed consent form, and have good compliance exclusion criteria: 1. no metastatic disease; 2. 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 3. received radiotherapy within 2 weeks before starting 6 months of darolutamide + docetaxel + adt treatment; 4. stroke, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass surgery, congestive heart failure (new york heart association class iii or iv); 5. history of malignant tumors; 6. planned receipt of other anti-tumor treatment during the study treatment period; 7. known allergy to the above drug components; 8. difficulty swallowing, chronic diarrhea, intestinal obstruction, and various factors affecting drug intake and absorption; 9. refusal to sign the informed consent form; 10. investigator's opinion that the participant is not suitable for inclusion.

Keywords: triple treatment regimen mhpsc darolutemide