Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Inclusion criteria

• 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.