Pivotal Study of MRI-guided Transurethral Ultrasound Ablation in Patients With Localized Prostate Cancer

Study Overview
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Brief Summary
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A prospective, multi-center, single-arm study, planned in 150 patients. The primary objective of the study is to further evaluate the safety and efficacy of a magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy system (TULSA-PRO) intended to ablate prostate tissue of patients with localized, organ-confined prostate cancer.

Detailed Description
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Profound Medical Inc. has developed a novel technology called the MRI-guided transurethral ultrasound therapy system (TULSA-PRO). The technology is developed for patients with organ confined prostate cancer. The therapeutic endpoint of this technology is thermal coagulation of prostate tissue. The treatment is conducted within a MRI suite, which enables real-time temperature images of the heated region to be acquired as the ultrasonic treatment is delivered. Using MRI thermometry during treatment, dynamic temperature feedback control over the intensity of the ultrasound beams and rotation of the Ultrasound Applicator can shape the pattern of thermal coagulation accurately and precisely in the prostate gland. It provides advantages of a non-invasive procedure with short treatment times.

Official Title
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Evaluation of the TULSA-PRO MRI-Guided Transurethral Ultrasound Prostate Ablation Device in Patients With Localized Prostate Cancer: a Prospective, Single-Arm, Pivotal Clinical Study

Conditions
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Prostate Cancer

Intervention / Treatment
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* Device: MRI-guided Transurethral Ultrasound Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, age 45 to 80 years Biopsy-confirmed adenocarcinoma of the prostate. Biopsy (minimum 10 cores) obtained ≥ 6 weeks and ≤ 6 months before treatment (or at the discretion of PI and approval by the Sponsor). Clinical stage ≤ T2b 4.1 Gleason score ≤ 3 + 4 (Part I only) 4.2 Gleason score 3+4 (Part II only) *now recruiting 5. PSA ≤ 15 ng/ml 6. Eligible for MRI [Form GCP-10131] 7. Eligible for general anesthesia (ASA category ≤ 3) 8. Prostate volume ≤ 90 cc, on Baseline MRI 9. Prostate size ≤ 5.0 cm in sagittal length, and ≤ 6.0 cm in axial diameter, on Baseline MRI 10. Life expectancy ≥ 10 years 11. No calcifications in the planned ultrasound beam path, or at the discretion of the investigator with approval from the Sponsor. Exclusion Criteria: Evidence (including Baseline MRI and bone scan) of extracapsular extension, sphincter involvement, seminal vesicle invasion, lymph node invasion or metastases Suspected tumour on Baseline MRI within 3 mm of the prostatic urethra, or in the prostate apex within 3 mm from the sphincter plane Prior definitive treatment of prostate cancer Prior transurethral resection of the prostate (TURP) Use of 5-alpha reductase inhibitors (5-ARIs) or hormone therapy within 3 months prior to the baseline visit. Baseline PSA must be established after a minimum of 3 months following 5-ARIs discontinuation. Additionally, use of 5-ARIs is not permitted following treatment during the study follow-up period. Prostate calcifications > 1 cm in largest diameter, on Baseline Ultrasound Cysts > 1 cm in largest diameter, on Baseline MRI Bleeding disorder (INR > ULN and PTT > ULN) Abnormal coagulation and current anticoagulant therapy. Patients whose anticoagulation therapy can be temporarily reversed within 7 days prior to treatment are eligible. Platelet inhibitors (ie: ASA) and heparin are not exclusion criteria. Acute unresolved Urinary Tract Infection (UTI) Interest in future fertility History of any other malignancy other than skin cancer, or low grade bladder cancer which has been completely resected, within the previous 2 years. Patients that have had curative treatment of a previous malignancy and no recurrence of that malignancy within the past 2 years will be allowed. Patients with peripheral arterial disease with intermittent claudication or Leriches Syndrome Patients with diabetes who have evidence of complications from their diabetes, such as end organ sequelae of diabetes or Hemoglobin A1c > 7%. History of any major rectal or pelvic surgery or radiotherapy History of ulcerative colitis or other chronic inflammatory conditions affecting rectum (includes rectal fistula, anal stenosis) Documented clinical prostatitis requiring therapy within 6 months prior to Treatment History of urethral and bladder outlet disorders, including urethral stricture disease, urethral diverticulae, bladder neck contracture, urethral fistulae, urethral stenting, urethral sling, urethroplasty or chronic indwelling urethral catheter Patients with artificial urinary sphincter or any penile implant Severe neurogenic bladder Untreated bladder stones History of acute urinary retention within the last 12 months Active untreated gross hematuria for any cause Post Void Residual (PVR) bladder volume > 250 mL Obstructing median lobe enlarged out of proportion to the rest of the prostate and protruding significantly into the bladder, sometimes referred to as ball valve median lobe, determined on Baseline MRI Any prostate related investigational therapy within 6 months of Visit 1 History of Parkinson's disease or multiple sclerosis History of drug abuse Known infectious disease including HIV positivity or AIDS-related illness, HBV and HCV Current unilateral or bilateral hydronephrosis Allergy or contraindications to administration of the GI anti-spasmodic drug: Patients in the USA: Glucagon Patients in Canada and Europe: Buscopan (Hyoscine) Contraindications to administration of gadolinium-based MRI contrast agent (e.g. Magnevist), such as chronic, severe kidney disease, acute kidney injury, history of Sickle Cell Disease, history of anemia, or intolerance/allergy to the contrast agent Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRI-guided Transurethral Ultrasound Ablation Device<br>Magnetic resonance imaging-guided transurethral ultrasound ablation of whole-gland prostate tissue. | Device: MRI-guided Transurethral Ultrasound Ablation<br>* Magnetic resonance imaging-guided transurethral ultrasound ablation is a novel minimally-invasive procedure where the therapeutic endpoint is prostate ablation through thermal coagulation.<br>* Other names: TULSA-PRO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint - Incidence of treatment-emergent adverse events | Frequency and severity of all adverse events will be evaluated by attribution and reported in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) standard published by the National Cancer Institute (NCI). | 1 year | 
| Efficacy Endpoint - Proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. | Prostate ablation efficacy will be evaluated using the proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erectile Dysfunction Endpoint | Rate of erectile dysfunction, determined by the change from baseline of the proportion of patients with IIEF-5 < 17. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| Erection Firmness Endpoint | Rate of erection firmness sufficient for penetration, determined by the change from baseline of the proportion of patients with IIEF item 2 ≥ 2. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| Urinary Incontinence Endpoint | Rate of urinary incontinence, determined by the change from baseline of the proportion of patients with EPIC item 5 ≥ 1 (one or more pads per day). | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| PSA Nadir Endpoint | Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml. | 1 year | 
| PSA Stability Endpoint | Proportion of patients with PSA ≤ 0.5 ng/ml at the most recent follow-up visit. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| Prostate Volume Endpoint | Prostate volume reduction, evaluated on MRI between the treatment day and 12-month follow-up visits. | 1 year | 
| Prostate Biopsy Endpoint | Proportion of patients with negative prostate biopsy at the 12-month follow-up visit, determined by transrectal ultrasound-guided 10-core biopsy. | 1 year | 
| IPSS Endpoint | Change in International Prostate Symptom Score (IPSS), between the baseline and most recent follow-up visit. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| IIEF Endpoint | Change in the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains of the International Index of Erectile Function (IIEF-15), between the baseline and most recent follow-up visit. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| EPIC Endpoint | Change in Urinary, Bowel, Sexual and Hormonal domains of the Expanded Prostate Cancer Index Composite (EPIC), between the baseline and most recent follow-up visit. | At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years). | 
| Targeting Accuracy Endpoint | Conformal prostate ablation, measured quantitatively between the target prostate volume and the target temperature isotherm on MRI thermometry acquired during the TULSA-PRO procedure, and described using three measures of targeting accuracy (Dice Similarity Coefficient; Over- and under-targeted volumes; Linear targeting in mm). | During treatment | 
| CE-MRI Endpoint | Conformal prostate ablation, assessed qualitatively by visualizing the peripheral region of enhancement surrounding the non-perfused volume (NPV) on contrast-enhanced (CE)-MRI acquired immediately after treatment. | Immediately after treatment | 
| mpMRI Endpoint | Characterize the effect of the TULSA-PRO ablation on diagnostic multi-parametric prostate MRI (mpMRI), determined using PI-RADS v2 performed at the Baseline and 12-month follow-up visits. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, high intensity transurethral ultrasound ablation, MRI-guided, minimally invasive, real-time temperature feedback control, whole-gland, TULSA