Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Prior treatment

• Prior systemic therapy for metastatic castration-resistant disease
• Prior chemotherapy for mHSPC, except docetaxel
• Prior LuPSMA or radium 223 for prostate cancer
• Concomitant or recent (within 28 days of registration) treatment with any other experimental drug
• Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control and GnRH analogues
• Acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days before expected start of treatment
• Any concomitant drugs contraindicated for use with darolutamide according to the approved product information

Other illness

• Severe or uncontrolled cardiovascular disease
• Known hypersensitivity to darolutamide
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of darolutamide
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Other

• Presence of a small cell component
• Clinical or radiological evidence of current spinal cord compression

• Written informed consent according to Swiss law and ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate
• Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues (agonists or antagonists).
• Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial
• Metastatic disease, documented by imaging according to PCWG3 criteria
• Measurable disease or bone lesions that are evaluable according to PCWG3 criteria
• A minimum of 12 months on ADT+ARPI therapy (calculated from ADT initiation) within mHSPC setting, showing an at least 50% PSA response or partial remission according to RECIST v1.1. ARPI change within mHSPC is only allowed for intolerance.
• Progressive disease according to modified PCWG3 before registration is defined as (at least 2 out of 3):
  • PSA progression ≥ 25% above nadir (2 consecutive rises at least 3 weeks apart)
  • New metastatic lesion on imaging (at least two or more new bone lesions on bone scan or one new non-bone lesion or progression on PSMA-PET/CT according to PROMISE V2 criteria
  • Clinical progression
• Patients with a previously treated malignancy are eligible, when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low
• Age ≥ 18 years
• WHO performance status 0-2
• Adequate bone marrow function: absolute neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L.
• Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), ALT and AST ≤ 2.5 x ULN, or ≤ 5 x ULN under the assumption that abnormal values are a result of cancer
• Adequate renal function: estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73 m2 (according to CKD-EPI formula)
• Men agree not to donate sperm or to father a child during trial treatment and until 3 months after the last dose of trial treatment
• Patients are able and willing to swallow darolutamide as whole tablet.