Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC

Study Overview
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Brief Summary
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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.

Detailed Description
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Patients will firstly receive 6 months of darolutamide in combination with docetaxel and ADT treatment. 1. 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. 2. 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

Official Title
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Randomized Controlled Study on the Efficacy and Safety of Intermittent Darolutamide Treatment in the Triple Therapy of Metastatic Hormone Sensitive Prostate Cancer

Conditions
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Metastatic Prostate Cancer, Intermitent Anti-androgen Therapy

Intervention / Treatment
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* Drug: Darolutamide continuous
* Drug: Darolutamide intermittent


Participation Criteria
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Eligibility Criteria
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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. (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): Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN Total bilirubin (TBIL) ≤ 2.0 × ULN; Serum creatinine (Cr) ≤ 2.0×ULN; 7. 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two independent arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continuous treatment group<br>Darolutamide: 600mg, bid+ADT: Leuprorelin (3.6mg qm or 10.8mg q3m) or goserelin 80mg qm until mCRPC | Drug: Darolutamide continuous<br>* standard of care<br>* Other names: Darolutamide;|
| Experimental: Intermittent treatment group<br>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. | Drug: Darolutamide intermittent<br>* experimental group<br>* Other names: Darolutamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression Free Survival | rPFS | 36 months | 
| Overall Survival | OS | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to castration-resistant prostate cancer | Time to mCRPC | 36 months | 
| Time to pain progression | TTPP | through study completion, an average of 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Darolutemide, triple treatment regimen, mHPSC