ACTinium in Castrate-RESistant Prostate Cancer After LUTEtium
brief summary
Advanced metastatic castration-resistant prostate cancer is a medical condition for which additional effective and tolerable treatments are urgently needed in order to improve patient outcomes and quality of life. The goal of this clinical trial is to learn more about Actinium (225Ac) radiohybrid prostate-specific membrane antigen-10.1 (rhPSMA-10.1) injection in men with prostate cancer that has spread and progressed after previous treatments, particularly after Lutetium-PSMA. Actinium (225Ac) rhPSMA-10.1 is an injectable radioactive medication that aims to attach to prostate cancer cells in the body and destroy them using ionising radiation. It is a new medication that has not yet been studied in humans. Participants will receive a dose of Actinium (225Ac) rhPSMA-10.1 every 6 weeks, to a maximum of 6 doses. They will be reviewed regularly by the trial researchers to monitor side effects and safety signals. A range of medication doses will be administered so that researchers can find out what doses of the medication are safe for men with prostate cancer. The trial will also aim to determine how effective this medication is for treating advanced prostate cancer.
detailed description
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.
official title
A Multi-site, Prospective, Open-label Phase I/II Trial of Actinium (225Ac) rhPSMA 10.1 to Evaluate Safety and Anti-tumour Activity in Men With Metastatic Castrate-resistant Prostate Cancer (mCRPC) Including Those Who Have Previously Responded to Lutetium-PSMA