A novel treatment strategy combining darolutamide and radium-223 is considered for subjects with mCSPC. Response to treatment is monitored every 12 weeks using a continuous measurement. The main scientific question concerns the comparison of radium-223 to placebo and is best addressed by a randomized clinical trial. Use of placebo in this study is considered ethical, as provision is made for subjects to discontinue their treatment and switch to radium-223 due to lack of efficacy on unblinding where it influences current treatment decisions. Switch to rescue medication is an intercurrent event, after which it is still possible to collect the variable measurements as described in sections on study endpoints below. This is also the case after other intercurrent events such as discontinuation of radium-223 treatment due to an adverse event, but not for intercurrent events such as death unrelated to study IP or disease, subject loss to follow-up, or subject withdrawal from all study treatments and procedures.
The goal of this clinical trial is to compare the combination of Darolutamide with Radium-223 or placebo and the effects on radiological progression-free survival for patients with Metastatic Castration-Sensitive Prostrate Cancer (mCSPC)~The main questions it aims to answer are:~Radiological progression-free survival (rPFS) in mCSPC~Overall Survival (OS)~Symptomatic skeletal event-free survival (SSE-FS)~Initiation of subsequent antineoplastic therapy~Safety~Participants will have visits at baseline, treatment is once a month for up to 6 months, and long term follow up will continue until the participant dies, withdraws consent, and/or study is terminated.