Evaluating Hormone Therapy to Achieve Optimal Doses in Metastatic Prostate Cancer

NCT07751133 | Recruiting Phase 3 DMC

• 3 other identifiers: UCL/199231CRCCTM-May25/100007IRAS ID: 1011482
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• 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).

Conditions

Prostate Cancer; mHSPC; mCRPC

Keywords

Prostate cancer; Metastatic; ARPI; ADT; Androgen Receptor Pathway Inhibitor; Androgen Deprivation Therapy

Outcome Measures

Primary Outcomes (3)

• Overall survival (primary efficacy)

  Overall survival, defined as the time from date of randomisation to date of death from any cause, and those who are alive are censored at the date last known to be alive. This will be assessed for non-inferiority using a margin for the absolute risk difference at 2 years of ≤4 percentage points, between reduced and standard dose ARPI arms. A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

  From randomisation up to 6 years (or date last known to be alive) or date of death, whichever occurs first.

• The percentage of patients who permanently discontinue ARPI due to adverse events

  Adverse events will be analysed using CTCAE Version 6.0 categorisation (all grades) for patients who permanently discontinue APRI. A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

  From start of treatment to permanent discontinuation of trial treatment up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

• Fatigue assessed using the EORTC 12-point fatigue scale (primary toxicity)

  Fatigue assessed using the EORTC 12-point fatigue scale (QLQ-FA12). A hierarchical approach will be applied to all 3 primary outcome measures, in which each analysis (in turn) should yield a p-value of \<0.05 in the following ranked order: 1. Non-inferiority for overall survival 2. Superiority of a mean difference in QoL fatigue score (expected to be ≥7 units) 3. Superiority for the percentage of patients who do not discontinue ARPI due to adverse events

  Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.

Secondary Outcomes (10)

• Toxicities using the CTCAE v6 categorisation (all grades).

  From date of consent to 30 days post last IMP dose administration.

• Failure-free survival (FFS)

  From randomisation until disease progression or death up to 6 years after first patient enrolled.

• Measures of progression (rising PSA, and locally defined clinical and radiological progression), at 1 and 2 years post-randomisation.

  From randomisation to date of documented objective disease progression, assessed up to 2 years post-randomisation.

• Adherence: the proportion of patients who stop ARPI permanently due to reasons other than disease progression, at 1 and 2 years.

  From randomisation to 2 years post-randomisation.

• Adherence: the duration of ARPI.

  From start of treatment to permanent discontinuation of trial treatment up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Standard Dose = Standard recommended (100%) dose of ARPI (enzalutamide, apalutamide, darolutamide or abiraterone).

Drug: Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy

Interventional Arm

EXPERIMENTAL

Reduced Dose = Reduced dose (50%) of the standard recommended dose of ARPI (enzalutamide, apalutamide, darolutamide or abiraterone).

Drug: Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy

Interventions

Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy DRUG

ARPI therapy (Abiraterone, Apalutamide, Enzalutamide or Darolutamide) selected by local investigator per standard of care

Also known as: Goserelin, Leuprolide, and Triptorelin, Degarelix or Relugolix (ADT therapy per standard of care)

Control Arm; Interventional Arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male sex at birth
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• Prostate Cancer UK: collaborator
• University of Manchester: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

abiraterone; apalutamide; enzalutamide; darolutamide; Therapeutics; Goserelin; Leuprolide; Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Ananya Choudhury, Professor

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ENHANCE Trial Manager

CONTACT

+44 (0) 207 679 9898; ctc.enhance@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2026
• First Posted: August 7, 2026
• Study Start: August 28, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2033
• Last Updated: September 4, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)