NCT06401980 Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 162 participants in total. It began in 2024-10-22 with a primary completion date of 2030-06.

Brief Summary

Despite improvements in treatment, metastatic prostate cancer remains incurable, especially in the case of pretreated metastatic castration-resistant disease (mCRPC), where treatment options are limited, leading to an unmet need. The paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has affected the treatment landscape for mCRPC patients. Many have already received androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI), making first-line mCRPC treatment challenging. The Swiss Group for Clinical Cancer Research (SAKK) has shown in previous studies that maintenance treatment with an ARPI, such as darolutamide, can improve radiographic progression-free survival (rPFS) in pretreated mCRPC patients. In the SAKK 08/16 trial, darolutamide maintenance was found to prolong PFS compared to placebo, especially in patients who responded well to prior ARPI treatment. Based on these findings, the hypothesis is that continued AR-pathway blockade with darolutamide, initiated in patients progressing from mHSPC to mCRPC on ARPI treatment, can improve outcomes when added to standard first-line mCRPC therapy and continued as maintenance. The proposed study aims to evaluate the efficacy of darolutamide, combined with physician-choice standard of care (including taxane chemotherapy, olaparib, radium 223, or LuPSMA), followed by maintenance therapy, on rPFS for patients in the first-line setting of mCRPC.

Eligibility Criteria

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. Exclusion Criteria: * Presence of a small cell component * 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 * Severe or uncontrolled cardiovascular disease * Acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days before expected start of treatment * Clinical or radiological evidence of current spinal cord compression * Any concomitant drugs contraindicated for use with darolutamide according to the approved product information * 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.

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