Prospective Clinical Safety and Efficacy Study of Lesion-targeted MRI-TULSA for Localized Prostate Cancer

Study Overview
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Brief Summary
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Magnetic resonance imaging (MRI) has improved detection of clinically significant prostate cancer (PCa). MRI-guided transurethral ultrasound ablation (MRI-TULSA) system incorporates precise diagnosis and simultaneous ablation of prostate tissue enabling lesion-targeted treatment of PCa. Lesion-based treatment strategy spares surrounding healthy tissues from injury, which may improve the outcome of genitourinary function. This study further investigates the safety and the efficacy of lesion-targeted ablation of MRI-visible biopsy-proven PCa with MRI-TULSA.

Detailed Description
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Improving diagnostic methods and screening of men with prostate specific antigen (PSA) has led to earlier detection of prostate cancer (PCa) with more favorable disease characteristics. To decrease overtreatment, low risk cases are increasingly treated with active surveillance; nevertheless some of them progress requiring interventions. Intermediate- and high-risk cases need active treatments to improve survival. However, despite desirable local control, the standard therapies including radical prostatectomy and radiation therapy, carry a risk of treatment related adverse effects to genitourinary and bowel functions. There is an eminent need for efficient PCa therapies with minimal effect on genitourinary function and quality of life. To date most studied mini-invasive technologies have used extremities of temperatures to treat PCa including high intensity focused ultrasound and cryoablation. Magnetic resonance imaging (MRI) has improved PCa diagnosis. Novel MRI techniques enable localization and visualization of clinically significant PCa. Further, MRI can be used for guidance of targeted biopsy from suspicious lesion enhancing detection of clinically significant PCa and pinpointing a target for image guided therapies. Also, increased use of MRI may lead to more MRI-visible tumors encountered in clinical practice developing an unmet need for image guided therapies. MRI guided transurethral ultrasound ablation (MRI-TULSA) - treatment system offers treatment strategy incorporating precise diagnosis and targeted therapy. It has been evaluated for whole-gland ablation of localized PCa. Further, lesion-targeted MRI-TULSA has been proved to be feasible and safe for treating MRI-visible-biopsy-concordant histologically significant PCa in our phase 1 treat-and-3-week-resect study (not published yet). This current study further investigates the safety and the efficacy of lesion-targeted ablation of MRI-visible biopsy-proven PCa with MRI-TULSA.

Official Title
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Prospective Clinical Safety and Efficacy Study of Lesion-targeted MRI-guided Transurethral Ultrasound Ablation for Localized Prostate Cancer

Conditions
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Localized Prostate Cancer

Intervention / Treatment
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* Device: MRI-TULSA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Language spoken: Finnish, English or Swedish Mental status: Patients must be able to understand the meaning of the study Informed consent: The patient must sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff. Biopsy-confirmed acinar adenocarcinoma of the prostate Gleason score ≥ 3+4/International Society of Urological Pathology grade group ≥ 2 High volume Gleason score 6 as determined on biopsies (>2 positive cancer core or ≥ 50% cancer in a core) Patient presenting low volume Gleason score 6 disease and refuses active surveillance Non-metastatic disease; high-risk patients according to European Association of Urology risk group stratification will undergo F-Prostate specific membrane antigen-Positron Emission Tomography/Computer Tomography to exclude distant metastasis Lesion visible on MRI (Prostate Imaging Reporting and Data System v2 4-5) Eligible for general anesthesia (American Society of Anesthesiologists (ASA)≤ 3) Exclusion Criteria: Contraindications for MRI (cardiac pacemaker, intracranial clips etc.) Acute unresolved urinary tract infection Claustrophobia Hip replacement surgery or other metal in the pelvic area Known allergy to gadolinium Inability to insert urinary catheter Suspected tumor on baseline MRI further than 30 mm or within 3 mm of the prostatic urethra Prostate calcifications or cysts obstructing planned ultrasound beam path within the targeted tissue volume Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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: Lesion-targeted ablation with MRI-TULSA<br>Intervention: Targeted lesion based thermoablation of MRI-visible biopsy proven clinically significant prostate cancer. Ablative effect is aimed to cover lesion with 5 mm MRI based healthy tissue overlap wherever possible but not compromising viability of critical tissues, mainly the wall of rectum. | Device: MRI-TULSA<br>* The technology is developed to ablate targeted prostate tissue through transurethrally inserted probe that transmit ultrasound energy under MRI guidance and control. The therapeutic endpoint of this method is thermal coagulation of prostate tissue. TULSA-PRO (Profound Medical Inc, Toronto, Canada): PAD-105, integrated into a 3 Tesla MR-system (Ingenia 3.0 Tesla, Philips Healthcare, Best, Netherlands)<br>* Other names: MRI guided transurethral ultrasound ablation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe adverse event free survival | The primary safety outcome is the freedom from severe adverse events over 3 months follow up: Clavien Dindo Classification of surgical complication is graded from 1 (mild) to 5 (death). Severe adverse events are regarded as events graded ≥3. | 3 months | 
| Oncological efficacy: Disease free survival | The primary oncological efficacy outcome, disease free survival (DFS), is the freedom from any histologically proven clinically significant prostate cancer as assessed from both 10-12-core systematic biopsies and MRI-directed 2-4-core in field biopsies at 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary continence status | Urinary continence status as measured by Expanded Prostate Cancer Index Composite (EPIC) item 5 ≥ 2 (patient filled and reported outcome measure) | 3, 6 and 12 months | 
| Overall urinary symptom score | Symptom severity as measured by International Prostate Symptom Score (IPSS) (patient filled and reported outcome measure). Compared to baseline, score change of ≥ 4 is considered clinically significant. | 3, 6 and 12 months | 
| Erectile function sufficient for penetration | Erectile dysfunction status as measured by International Index of Erectile Function item 2 ≥ 2 (erection firmness sufficient for penetration)(patient filled and reported outcome measure). Not applicable for subject with baseline score < 2. | 3, 6 and 12 months | 
| Overall erectile function | Erectile function as measure by International Index of Erectile Function-5 (IIEF-5)(patient filled and reported outcome measure). Compared to baseline, score change of ≥ 4 is considered clinically significant. | 3, 6 and 12 months | 
| Radiological failure free survival | Presence of a highly suspicious lesion in treatment field on prostate MRI at 6 or 12 months (Likert suspicion level ≥ 4). | 6 and 12 months | 
| Ablation failure free survival | In field (ablated area) biopsy-confirmed histologically viable cancer. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Localized prostate cancer, Transurethral ultrasound ablation, Image guided, Magnetic resonance imaging guided, Lesion-targeted, Focal therapy