IP17- Apalutamide prior to Prostate ablation Of focal Lesions in patients with LOcalised prostate cancer
Localised prostate cancer
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 therapy. Participants will be randomised using Sealed Envelope on a 1:1 basis into one of two arms as per below. Control arm (Arm 1): Focal therapy alone (high intensity focused ultrasound [HIFU], irreversible electroporation [IRE] or cryotherapy) as per tumour characteristics. Intervention arm (Arm 2): Neoadjuvant apalutamide 240 mg orally once daily for 3 months (90 days) followed by focal therapy (as per control arm). During the treatment period, Patient Reported Outcome Measure (PROM) questionnaires will be completed. Following focal therapy, participants will be followed up 3-monthly for the first year and then 6-monthly from thereon. All participants will undergo an additional prostate biopsy at 6-12 months following their focal therapy treatment. For the pilot study, all participants will be followed up for at least 12 months. If the study proceeds into the main study, all participants will be followed up for 5 years or until the end of the study (whichever occurs first). PROMs will continue to be collected throughout the follow-up period.
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.
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 infa