Localised prostate cancer Cancer
Conditions
Interventions
Two-arm, adaptive randomised control trial (RCT) with an internal pilot and blinded interim analysis to compare PFS following focal therapy alone versus 3 months of neoadjuvant apalutamide and focal t
Sponsors
Imperial College London
Eligibility
Sex/Gender
Male
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. Age >/=18 years with no upper limit 2. PSA =20 ng/ml 3. MRI stage <=T3aN0M0. Broad capsular contact is permitted, macroscopic disease outside capsule is not.* 4. Overall Gleason =4+3 and maximal Gleason 4+4 within the targeted cores to allow for targeted biopsy artefact. Low volume (<4 mm) of Gleason 3+3 or 3+4 will be permitted outside of the lesion being treated. 5. Pathology should be concordant with a lesion on prostate MRI. 6. Fit for a general anaesthetic. 7. Can give informed consent *Patients must have undergone a diagnostic pre-biopsy MRI compliant with national uro-radiology consensus guidelines. Dynamic contrast enhancement using gadolinium is not required at diagnostic stage but will be required during follow-up.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 03/06/2026: 1. Locally advanced disease (macroscopic T3a or T3b+) that is not suitable for focal therapy 2. Life expectancy of less than 5 years 3. Unable to undergo a multiparametric 1.5 or 3T MRI 4. Previous treatment for prostate cancer, including hormonal therapy, radiotherapy or surgery (the use of 5-alpha reductase inhibitors is not an exclusion criterion) 5. History of seizures or other predisposing factors, including underlying brain injury, recent stroke (within 1 year), primary brain tumours or brain metastases 6. No contraindication to apalutamide* 7. Previous treatment with any investigational medicinal product or participation in another interventional clinical trial within 30 days prior to the first dose of study treatment. Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary. Hypersensitivity to anti-androgen therapy. Previous exclusion criteria: 1. Locally advanced disease (macroscopic T3a or T3b+) that is not suitable for focal therapy 2. Life expectancy of less than 5 years 3. Unable to undergo a multiparametric 1.5 or 3T MRI 4. Previous treatment for prostate cancer, including hormonal therapy, radiotherapy or surgery (the use of 5-alpha reductase inhibitors is not an exclusion criterion) 5. History of seizures or other predisposing factors, including underlying brain injury, recent stroke (within 1 year), primary brain tumours or brain metastases 6. No contraindication to apalutamide* Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary. Hypersensitivity to anti-androgen therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pilot Study: 1. Recruitment rate per centre per month measured at the end of each month until the final patient is recruited. 2. Acceptance of randomisation (rate-per-month per-centre average) and compliance to allocated arm measured at time of consent (acceptance to randomisation) and at time to treatment (compliance) Main Study: Progression-free survival (PFS), defined as the time from randomisation to the first incidence of further focal therapy or salvage whole-gland treatments (radiotherapy or surgery) or prostate cancer metastases (radiologically confirmed) or prostate cancer-specific mortality. Measured at time of progression or failure judged clinically or a maximum of 5 years follow-up after focal therapy. Should the study continue to the main phase, all patients (including those enrolled during the pilot) will continue follow-up over a total of 60 months and the endpoint will be assessed at the end of this period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pilot Study: 1. Pathological response rate as defined by any Gleason 3+4 or greater cancer on 6–12-month post- treatment protocol mandated control biopsies after the initial focal therapy session. 2. Pathological effect from 3 months of apalutamide determined on pre-focal therapy biopsies of the prostate 3. Genitourinary and rectal side-effects and quality of life metrics measured using validated patient-reported outcome measures (PROMs) and adverse events at time of consultation for study, after consent and after treatment at 6–12-month follow-up Main Study: Disease control: 1. Rate of positive biopsy for any cancer and significant cancer is measured using histology on biopsy prior to focal therapy (treated and untreated side) at baseline and after 3 months of neoadjuvant Apalutamide 2. Rate of positive biopsy for any cancer and significant cancer is measured using histology on biopsy following focal therapy (treated and untreated side) at baseline and annually throughout the 5-year follow-up period 3. Rate of second or third focal therapy sessions (in-field or out-of-field) is measured using treatment records at baseline and annually throughout the 5-year follow-up period 4. Rate of radiotherapy as salvage therapy following focal therapy is measured using treatment records at baseline and annually throughout the 5-year follow-up period 5. Rate of prostatectomy as salvage therapy following focal therapy is measured using treatment records at baseline and annually throughout the 5-year follow-up period 6. Rate of systemic therapy as salvage therapy following focal therapy is measured using treatment records at baseline and annually throughout the 5-year follow-up period 7. Metastases-free survival is measured using imaging and clinical records at baseline and annually throughout the 5-year follow-up period 8. Prostate cancer-specific mortality is measured using death certificates and clinical records at baseline and annually throughout the 5-year follow-up p | — |
Countries
England, United Kingdom
Contacts
Public ContactAmalia;Tayla Ndoutoumou;Perreau
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Outcome results
None listed