ACTinium in Castrate-RESistant Prostate Cancer After LUTEtium

This is a multi-site, prospective, open-label Phase I/II trial of Actinium (225Ac) rhPSMA-10.1 for men with metastatic castration-resistant prostate cancer (mCRPC). The novel ligand radiohybrid (rh) PSMA-10.1 has shown favourable properties in early clinical and preclinical studies. As an emitter of alpha-radiation, Actinium-225 is expected to deposit greater energy at a shorter range than beta-emitting Lutetium-177, conferring the potential to overcome prior PSMA-based radioligand therapy failure. Phase I of this trial will focus on dose-finding and medication safety. It will investigate men with mCRPC who have previously responded to Lutetium-PSMA, however, a small number of participants will be permitted to be Lutetium-PSMA-naïve. Participants will additionally be assessed for early signals of treatment activity and there will also be an exploratory dosimetry component. Phase II will utilise the dose selected from Phase I and expand the treatment cohort. In Phase II all participants are required to have previously responded to Lutetium-PSMA. Study participants must all undergo a screening process and meet trial criteria before they begin any treatment. Provided they tolerate treatment well and their prostate cancer does not worsen during treatment, participants will be offered further treatment every six weeks, to a maximum of six doses. Study participants will be reviewed weekly by a trial doctor to ensure they are tolerating treatment well and that any potential side effects of the treatment are identified and addressed. These reviews will sometimes be done remotely e.g. on the phone. Monitoring blood tests will be done regularly, and in Phase II this will also include collection of blood samples for exploratory genetic analysis. After starting treatment, participants will have a CT and bone scan every 12 weeks in order to assess whether their prostate cancer sites are responding to treatment. After trial treatment is complete, participants will be asked to remain on follow-up to help build an understanding of any long-term impacts of the treatment.