Evaluating Hormone Therapy to Achieve Optimal Doses in Metastatic Prostate Cancer

The goal of this phase 3 clinical trial is to determine the clinical effectiveness and cost effectiveness of using lower doses of Androgen Receptor Pathway Inhibitors (ARPI) to treat patients with prostate cancer that has spread (metastasized). The main questions it aims to answer are:

1. if overall survival for reduced dose ARPI is not worse than standard dose ARPI when treating patients with metastatic prostate cancer, and
2. that fatigue (extreme exhaustion) and not stopping ARPI permanently (due to adverse effects) are better than average with the reduced dose.

Participants will:

• Be randomised to take full dose (100%) of ARPI or half dose (50%) of ARPI.
• Receive standard of care ADT.
• Be on treatment for approximately 3 years according to standard of care.
• Have clinic assessments and visits in clinic or remotely, as per their treating hospital's standard routine local practice in line with standard of care. Additional visits are not expected.
• Complete quality of life questionnaires at week 0 (pre-treatment) and weeks 4, 16, 32, 48 and 64.
• Keep a diary of their symptoms.

Translational research samples will be collected as follows:

• Blood samples at week 0 (pre-treatment) and weeks 24, 32, 48 and at disease progression.
• Urine samples at week 0 (pre-treatment) and week 24 and at disease progression.
• FFPE Tumour: Routinely collected diagnostic blocks. The duration of follow-up is approximately 3 years after the last patient is recruited (minimum follow-up is 3 years; maximum follow-up is approximately 6 years for the the first patient recruited) and the trial is expected to complete August 2032 (Last Patient Last Visit).