Dose Optimisation and Prostate-Specific Membrane Antigen (PSMA) Receptor intensification with 177Lu-PSMA Therapy: A Randomised Phase II trial: OPTIMAL-PSMA

This study is testing a new dosing schedule of Lutetium-177 PSMA (177Lu-PSMA), a radioactive treatment for men with prostate cancer that has spread and no longer responds to standard hormone therapy. The aim is to see whether giving 177Lu-PSMA more frequently at the start of treatment can overcome early resistance and improve outcomes. Who is it for? You may be eligible for this study if you are a male aged 18 or over who has prostate cancer that has spread to other parts of the body and is no longer controlled by standard hormone therapy (castration-resistant). You must have evidence of metastatic disease on imaging, a reasonable general health status (ECOG 0–2), a life expectancy of at least 12 weeks, and adequate blood and organ function. Men who have previously received modern hormone therapies such as abiraterone or enzalutamide may be eligible. Study details All participants will be randomised to either arm 1 or arm 2 with different dosing schedules. Depending on when you join the study, you will either receive 7.5 GBq or 8.5 GBq. The first 40 participants randomised on the study (both arms 1 and 2) will all receive 7.5 GBq of 177 Lu-PSMA at each dosing visit. For the next 80 participants (participants 41 – 120), anyone randomised to arm 1 on the study will receive 8.5 GBq of 177 Lu-PSMA at each dosing visit. Participants will receive 177Lu-PSMA treatment according to either the standard schedule or a more frequent dosing schedule. You will have PSMA PET/CT scans, blood tests, and other routine health checks to monitor your response and side effects. It is hoped that this study will help provide important information on whether a new dosing schedule can improve the effectiveness of 177Lu-PSMA and guide future treatment for men with advanced prostate cancer.