A Phase 3 interventional study of Abiraterone, Apalutamide, Enzalutamide or Darolutamide (ARPI therapy) (per standard of care) therapy in Prostate Cancer, mHSPC and mCRPC, sponsored by University College, London. Recruiting at 4 sites in United Kingdom. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by University College, London · Phase 3, Interventional, and Treatment
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:
Participants will:
Translational research samples will be collected as follows:
ENHANCE is a clinical trial in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (mCRPC) who are clinically suitable for and planned to commence Androgen Receptor Pathway Inhibitors (ARPI) plus standard Androgen Deprivation Therapy (ADT).
Participants will be randomised according to the trial's stratification criteria to receive standard recommended (100%) dose or reduced dose (50%) of ARPI (enzalutamide, apalutamide, darolutamide or abiraterone) and take ADT.
Participants will have hospital clinic visits according to the trial visits assessment schedule as detailed in the trial protocol and in line with the recruiting centers standard of care policy.
Participants will complete questionnaires and keep a symptoms diary in accordance with the assessments schedule.
Participants will provide urine, blood and tumour diagnostic biopsy samples for translational research purposes according to the assessments schedule which will be sent to and processed by a Central Laboratory located in Manchester.
7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.
This study's planned enrollment of 1,500 is above the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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)
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
Time frame: 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
Time frame: 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
Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.
Toxicities using the CTCAE v6 categorisation (all grades).
Toxicities using the CTCAE Version 6.0 categorisation (all grades). Events that would be of special interest include hypertension, rash, hot flushes, cardiovascular events, and falls.
Time frame: From date of consent to 30 days post last IMP dose administration.
Failure-free survival (FFS)
Failure-free survival (FFS) defined as the time from the date of randomisation to the date of the first of the following forms of treatment failure: biochemical (prostate-specific antigen (PSA)) failure; progression of local, lymph-node, or distant metastases; starting another line of therapy, or death from prostate cancer. Patients without an FFS event would be censored at the date last known to be alive. Stopping treatment for reasons other than the events listed above would not be considered an FFS event.
Time frame: 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.
* Proportion of patients who have rising PSA (PSA progression is defined as ≥25% increase and at least a 2 ng/mL absolute increase above the nadir, confirmed by a second value ≥3 weeks later) at 1 and 2 years post randomisation. * Proportion of patients who have PSA only progression: PSA rise of ≥25% above lowest PSA result compared to baseline at 1 and 2 years post randomisation. * Proportion of patients who have significant clinical progression, including new cancer related symptoms, as determined by the local clinical team: at 1 and 2 years post randomisation. * Proportion of patients who have radiological progression as determined by the local clinical team: at 1 and 2 years post randomisation. * Proportion of patients who achieve PSA nadir of \<0.2 within 12 months of starting therapy (primarily for mHSPC patients).
Time frame: 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.
Adherence: proportion of patients who stop ARPI permanently due to reasons other than disease progression, at 1 and 2 years (reasons will be recorded).
Time frame: From randomisation to 2 years post-randomisation.
Adherence: the duration of ARPI.
Adherence: the duration of ARPI (in months) from the time of starting therapy.
Time frame: 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).
Proportion of patients who have a dose reduction of ARPI (from their starting dose, in either arm) due to adverse events.
Proportion of patients who have a dose reduction of ARPI (from their starting dose, in either arm) due to adverse events.
Time frame: From start of treatment to documented dose reduction of trial treatment due to adverse events up to 3 years after last patient is recruited (approximately 6 years for the first patient recruited).
Proportion of patients (dose reduction arm) who have their dose increased.
Proportion of patients (dose reduction arm) who have their dose increased (reasons will be recorded).
Time frame: 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).
Health-related quality of life using the EORTC QLQ-C30 questions
Quality of Life assessments will be undertaken using EORTC QLQ-C30 questionnaire using Likert score (26 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much; 2 questions scored: 1-7, 1=very poor, 7=excellent). Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.
Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.
Health-related quality of life using the EORTC QLQ-IL249 questions
Quality of Life assessments will be undertaken using EORTC QLQ-C30 which will include QLQ-IL249 questions using Likert score (22 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much). Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.
Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.
Health-related quality of life using the Euro-Qol-5D-5L (EQ-5D-5L)
Quality of Life assessments will be undertaken using EQ-5D-5L (self-reported) questionnaire using a combination of Likert score (5 questions with 5 dimensions of abilities) and visual analogue score (scored 0-100, 0=worst, 100=best). Descriptions of mean change in EQ-5D-5L scores will be presented and compared to baseline values from pre-treatment.
Time frame: Pre-treatment, Weeks 16, 32, 48 and 64 from start of treatment.
Plan to share: No — Data will not be shared until analysed and used as part of the study at which point data access will be considered with the researchers.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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