NCT05771896

Darolutamide With Radium-223 or Placebo and the Effect on Radiological Progression-Free Survival for Patients With mCSPC

A Phase III Randomized Study Comparing the Combination of Darolutamide With Radium-223 or Placebo and the Effect on Radiological Progression-Free Survival for Patients With Metastatic Castration-Sensitive Prostrate Cancer (mCSPC)

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: GenesisCare USA · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Metastatic Prostate Cancer

Interventions

Type	Name	Description
DRUG	Darolutamide	Participants will continue treatment with darolutamide until radiological progression, withdrawal, death, termination, or study completion. The maximum time for darolutamide dose interruption period is 28 consecutive days beyond scheduled dose (\>56 days between cycles). Any participant requiring dose interruption \>28 consecutive days beyond the scheduled dose may restart treatment with darolutamide if clinical benefit is anticipated and after discussion with and approval from the study Medical Monitor. Until primary endpoint is reached, participants are not allowed to switch ARPI (Abiraterone, Apalutamide or Enzalutamide) during the study. Switching to other ARPI following radiographic progression should be considered a subsequent life prolonging therapy and documented accordingly.
DRUG	Radium-223	Radium-223 should be given for 6 cycles, administered IV on Day 1 of each cycle or until radiological progression, withdrawal, death, termination, or study completion. The placebo will be administered in precisely the same fashion as the active drug. Subsequent cycles 2-6 should be scheduled to occur every 28 ± 7 days following the previous cycle, but dosing may be delayed up to 28 days per cycle (maximum 56 days between cycles). Any participant requiring dose interruption \>28 consecutive days (\>56 days between cycles) may restart treatment with radium-223/placebo if clinical benefit is anticipated and after discussion with the Medical Monitor. Participants will continue with darolutamide irrespective of Radium-223 administration. Upon radiological progression, further treatments are decided by the site investigator according to standard local practice.

Timeline

• Start date: 2023-09-01
• Primary completion: 2028-12-01
• Completion: 2029-04-01
• First posted: 2023-03-16
• Last updated: 2023-09-14

Regulatory

• FDA-regulated drug study