DAROLUTAMIDE for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years;\n- A confirmed diagnosis of progressive mCRPC (progression according to Prostate cancer Working Group (PCWG) 3 criteria), with an indication for docetaxel or cabazitaxel. Progression defined as ≥ 1 of the following 3 criteria: a. Radiographic disease progression in soft tissue per RECIST v1.1 b. Radiographic disease progression in bone defined by the appearance of ≥ 2 new bone lesions on bone scan. c. PSA progression defined as ≥ 2 sequential rises in PSA obtained ≥ 1 week apart with a minimal starting value of ≥ 1 ng/mL. A PSA value ≥ 2 ng/mL is required at study entry.\n- Patients should have had disease progression previously on at least one ARSi (abiraterone, apalutamide, darolutamide or enzalutamide). ARSi administration is allowed both in the mCNPC and in the mCRPC setting. Coadministration of docetaxel in mCNPC (triplet-therapy) is allowed.\n- WHO performance ≤ 2 (see appendix A)\n- Able and willing to sign the Informed Consent Form prior to screening evaluations\n- Adequate haematological, renal and liver function and chemistry, defined as: a. Hemoglobin ≥ 6.0 mmol/L b. Platelets ≥ 100 x 109/L c. ALT/AST ≤ 3x ULN and ≤ 5x ULN in case of liver metastases d. Creatinine clearance ≥ 50 ml/min e. Serum testosterone ≤ 1.7 nmol/L"}

Exclusion criteria

• {"criterion_text":"- Impossibility or unwillingness to take oral drugs\n- Hypersensitivity to taxanes\n- Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure, serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases)\n- Symptomatic peripheral neuropathy CTCAE grade ≥2\n- Docetaxel-rechallenge."}

Primary endpoints

• {"endpoint_text":"- The main study endpoint is progression free survival, which is defined as time from randomization to radiologic, biochemical or pain progression or death from any cause, whichever occurs first, according to PCWG3 (Appendix C).","definition_or_measurement_approach":"Time from randomization to radiologic, biochemical or pain progression or death from any cause, whichever occurs first, according to PCWG3."}

Secondary endpoints

• {"endpoint_text":"- Overall survival, defined as time from randomization to death from any cause.","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"- Time to progression, defined as time from randomization to radiologic, biochemical or pain progression, whichever occurs first.","definition_or_measurement_approach":"Time from randomization to radiologic, biochemical or pain progression, whichever occurs first."}
• {"endpoint_text":"- The time to PSA progression, defined as time from randomization to biochemical progression.","definition_or_measurement_approach":"Time from randomization to biochemical (PSA) progression."}
• {"endpoint_text":"- The time to pain progression, defined as time from randomization to pain progression.","definition_or_measurement_approach":"Time from randomization to pain progression."}
• {"endpoint_text":"- The number and severity of adverse events","definition_or_measurement_approach":"Count and CTCAE grading of adverse events (no further measurement details provided in CTIS record)."}
• {"endpoint_text":"- Cell-free DNA aneuploidy scores and somatic aberrations in circulating tumor DNA","definition_or_measurement_approach":"Assessment of cfDNA aneuploidy scores and somatic aberrations in circulating tumor DNA (method not specified in CTIS record)."}
• {"endpoint_text":"- Differential expression of relevant genes, as measured in tissue and liquid biopsies. (comparing tissue and liquid biopsies at baseline and on-treatmen","definition_or_measurement_approach":"Differential gene expression measured in tissue and liquid biopsies at baseline and on-treatment (detailed assay/method not specified)."}
• {"endpoint_text":"- Immune subset phenotyping and subtyping as measured in tissue and whole blood","definition_or_measurement_approach":"Immune subset phenotyping and subtyping in tissue and whole blood (specific assays not detailed in CTIS record)."}

Netherlands

Earliest CTIS Part Ii Submission Date

23-10-2024

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

503

Number Of Sites

18

Number Of Participants

245

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands