Title: Magnetic Thermoablation in the Treatment of Early Prostate Cancer
Funder: Department of Health (England)

Abstract: Our proposal involves three work-packages that are inter-related with each following in a stepwise fashion with strict go/no-go points. Work-package 1. To evaluate the retention of magnetic microspheres in the prostate There is limited information on the retention of magnetic microspheres injected directly into the prostate. In previously irradiated prostates, there seems to be 90% particle retention. There is a need to determine the retention properties in treatment-naïve prostates. WP1 will enlist involve a phase I trial recruiting patients undergoing cystoprostatectomy surgery for bladder cancer (both bladder and prostate removed). The use of this prostate tissue to evaluate microsphere retention ( without thermoablation ) is possible without affecting these patients’ normal care. Patient Population Nine men undergoing cystoprostatectomy Intervention Injections of magnetic microspheres will be carried out through the perineal skin at varying volumes into each prostate lobe. Injection sites will start at 15mm from the posterior border of the prostate (3 patients) and injection sites moved posteriorly in 5mm increments (3 at 10mm, 3 at 5mm). Cross-sectional imaging will be carried out so that time-course of retention patterns can be evaluated. Comparator a) Cross-sectional imaging (CT and Mr.I) at prior to and at varying time-points after injection to determine retention of microspheres. b) Distribution of microspheres in ex-vivo prostate specimens using Perl staining Outcomes Primary : a) Safety and adverse events b) Percentage microsphere retention Secondary : a) Patient reported outcome measures (urinary, sexual, rectal) b) Distribution of microspheres compared with injection site in prostate c) Distribution in extra-prostatic areas Work-package 2. To construct a transrectal magnetic alternating current hyperthermia (MACH) probe The transrectal probe will be based on a pre-clinical MACH device that we have developed and validated in preclinical models. Our industry partner, RCL, will design and build a miniaturised 4-6cm diameter transrectal device which allows close apposition of the MACH applicator to the prostate (representing a significant innovation). It will implement a frequency-tracking modality to locate injection sites and position the MACH to deliver the magnetic field and monitor the frequency changes that arise from tissue heating. The latter will be carried out in a prostate phantoms and ex vivo prostate tissue (from WP1) in order to formulate a method by which temperature changes can be monitored in real-time. Work-package 3. To conduct a phase I safety and dose-finding trial using magnetic thermoablation to treat localised prostate cancer. We aim to recruit patients with low-risk prostate cancer to evaluate the safety, feasibility and optimal parameters of our magnetic thermoablation system to deliver discrete volumes of necrosis. Population Twenty patients with low-risk localised prostate cancer will be asked to participate. Intervention a) Multi-parametric Mr.I and template prostate mapping biopsies to localise and risk stratify cancer. b) Injection of magnetic microspheres with starting volume determined from WP1 (minimum acceptable level) and starting MACH field strength/duration determined from WP2. If treatment effect is safe with no serious adverse events, and depending on post-therapy imaging validation of ablative zone, injection volume will be increased or decreased. c) Injection volume and magnetic field parameters will be changed in an iterative manner until consistent and predictable ablative zones are seen. Outcomes Primary a) Safety and adverse events b) Toxicity: full blood count, serum renal and liver function Secondary a) Patient reported outcome measures (urinary, sexual, rectal) b) Feasibility of thermoablation and dose-finding assessed using - imaging (post-therapy contrast-enhanced Mr.I compared to pre-treatment). – biochemical (serum PSA at 1, 3 and 6 months) - histological (template transperineal biopsies at 6 months)


Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS