Evaluating Hormone Therapy to Achieve Optimal Doses in Metastatic Prostate Cancer

About This Trial

This clinical trial is for men whose prostate cancer has spread to other parts of the body and who are planning to start hormone treatment.
Researchers want to find out if taking half the standard dose of a common cancer-blocking pill works just as well as the full dose, while causing less extreme tiredness and fewer side effects.
If you choose to join, a computer will randomly assign you to take either the full dose or the half dose for about three years alongside your standard care.
Your doctor visits will mostly follow your normal clinic routine, but you will also be asked to keep a symptom diary, complete surveys about your quality of life, and give occasional blood and urine samples.

More Information

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).

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This clinical trial is for men whose prostate cancer has spread to other parts of the body and who are planning to start hormone treatment.

Study Details

Start Date: August 28, 2026
Lead Sponsor: University College, London

Full Eligibility Criteria

Inclusion Criteria

Adult males (male sex at birth) aged 18 years or older
Newly histologically or cytologically diagnosed prostate cancer (adenocarcinoma) that is metastatic hormone-sensitive (mHSPC) or metastatic castration resistant prostate cancer (mCRPC), for whom ARPI in combination with androgen deprivation is clinically planned
Prior ADT use for prostate cancer (including bilateral orchidectomy and transcutaneous oestrogen), is permitted provided: (a) ADT has been started less than 12 weeks prior to randomisation in mHSPC, (b) In the adjuvant setting the completion of adjuvant hormonal therapy was >12 months prior to randomisation and total duration is capped at 36 months total
ECOG performance status 0-2
Willing and able to give provide written informed consent.

Exclusion Criteria

Pathology other than adenocarcinoma consistent with small cell, ductal, sarcomatoid carcinoma of the prostate
Unable or unwilling to receive concurrent ADT alongside an ARPI
Any concurrent or previous malignancy that required active anti-cancer therapy in the previous 2 years of randomisation (other than basal cell or squamous cell carcinoma of the skin or adequately treated non-muscle invasive urothelial bladder carcinoma, Tis, Ta and T1 tumours)
Adults with unmanaged psychological, familial, or sociological conditions precluding them from the ability to provide informed consent or hampering compliance with the study follow-up, including continued drug and alcohol dependence
Patients who have received an investigational drug (either approved or not approved) in any prior clinical study within 30 days or 5 half-lives (whichever is longer) prior to Screening
Patients on triplet therapy (i.e. receiving additional systemic anti-cancer therapy such as chemotherapy, radionuclide/molecular radiotherapy, PARPi alongside ADT & ARPI); but concomitant radiotherapy is allowed
Hypersensitivity to any of the active components or excipients of the IMPs or NIMPs listed in this protocol
Patients with severe hepatic impairment (Child-Pugh Class C)
Patients with uncontrolled or unstable cardiovascular disease, New York Heart Association congestive cardiac failure class III/IV