MRI-guided Transurethral Urethral Ultrasound Ablation for the Treatment of Intermediate Grade Prostate Cancer

Study Overview
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Brief Summary
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This clinical trial tests whether the magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) procedure is safe and effective in treating patients with intermediate grade prostate cancer. TULSA ablation is a minimally invasive procedure that uses targeted ultrasound device to deliver high-frequency, electric current to kill cancer cells by heating them. The TULSA procedure may help patients avoid surgery and help improve prostate cancer patients' quality of life.

Detailed Description
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PRIMARY OBJECTIVE: I. To perform the TULSA procedure for safety and efficacy outcomes in men aged 45 to 80 years with biopsy-confirmed, National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer. SECONDARY OBJECTIVE: I. To assess patient-reported metrics for quality of life (QOL). II. To assess return to normal activity. III. Compare economic benefit as noted from Expanded Prostate Cancer Index Composite (EPIC) questionnaire. OUTLINE: Patients undergo MRI-guided TULSA. After completion of study treatment, patients are followed at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Official Title
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Focal Prostate Ablation for Intermediate Grade Cancer Utilizing TULSA Profound System

Conditions
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Prostate Carcinoma, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: MRI-Guided Transurethral Ultrasound Ablation
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age 45-80 years, with > 10 years life expectancy Biopsy-confirmed, NCCN (favorable Gleason grade [GG2] and unfavorable GG3) intermediate-risk prostate cancer Stage =< T2c, N0, M0 International Society of Urological Pathology (ISUP) grade group 2 or 3 disease on transrectal ultrasonography (TRUS-guided) biopsy (minimum 8 cores, combination of systematic and MRI fusion-guided) or in-bore biopsy (minimum 3 cores from each PI-RADS v2 category >= 3 lesion). Biopsy reported within 12 months of baseline visit, with minimum 6-week interval between biopsy and baseline PSA =< 20 ng/mL reported within 3 months of baseline Treatment naive Planned ablation volume < 3.0 cm axial radius from the urethra on mpMRI acquired within 6 months of baseline Exclusion Criteria: Inability to undergo MRI or general anaesthesia Suspected tumour > 30 mm from the prostatic urethra or < 14 mm from the prostatic urethra Prostate calcifications > 3 mm in maximum extent obstructing ablation of tumor on low-dose pelvic computed tomography (CT) Criteria subject to additional review and approval by sponsor. Alternatively, prospective TRUS to query calcifications or susceptibility-weighted MRI if available may be used to assess calcification. Imaging for calcification screening must be dated within 1 year of baseline visit Unresolved urinary tract infection or prostatitis History of proctitis, bladder stones, hematuria, history of acute urinary retention, severe neurogenic bladder Artificial urinary sphincter, penile implant or intraprostatic implant Less than 10 years life expectancy Patients who are otherwise not deemed candidates for radical prostatectomy (RP) Inability or unwillingness to provide informed consent History of anal or rectal fibrosis or stenosis, or urethral stenosis, or other abnormality challenging insertion of devices

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: Treatment (MRI-guided TULSA)<br>Patients undergo MRI-guided TULSA. | Procedure: MRI-Guided Transurethral Ultrasound Ablation<br>* Undergo MRI-Guided TULSA<br>* Other names: MRI-TULSA;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients free from treatment failure | Failure is defined as: delivery of any additional intervention for prostate cancer (local or systemic, including adjuvant therapy); or metastatic disease; or prostate cancer-specific death. | At 24 months post-treatment | 
| Proportion of patients who maintain both urinary continence and erectile potency | Continence is defined as 'pad-free' (0 pads/day), and potency is defined as erection firmness sufficient for penetration (Expanded Prostate Cancer Index Composite [EPIC]). Two-sided, 95% Pearson-Clopper confidence interval (CI) will be calculated for each intervention arm separately, and the difference in safety outcomes, along with exact 95% two-sided CI will be calculated. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical failure | In the absence of a validated threshold for biochemical failure in the setting of ablative therapies, the Phoenix criteria will be adopted for the transurethral ultrasound ablation (TULSA) procedure (nadir + 2 ng/mL). Prostate-specific antigen (PSA) is measured at baseline/procedure, 3, 6, 9, 12, 15, 18, 21, and 24 months. It's measured using Scale Grade Group 1, 2, 3, and 4. | Up to 24 months | 
| Histologic failure | The proportion of patients with clinically significant disease on targeted +/- systematic biopsy at 12 months. Clinically significant disease is defined as Gleason grade group 2 or higher. It is measured using scale Grade Group 1, 2, 3, and 4. | At 12 months | 
| Multiparametric magnetic resonance imaging (mpMRI) Prostate Imaging and Reporting and Data System (PI-RADS) version (v)2 score for each visible lesion | These data will also be collected at 24 months post-initial treatment, for patients who receive repeat TULSA procedure. Findings from for-cause mpMRI will also be captured using Pi-Rads 1-5, 1 being most likely not cancer to 5 being very suspicious. | At 24 months post-treatment | 
| Total prostate volume | These data will also be collected at 24 months post-initial treatment, for patients who receive repeat TULSA procedure. Findings from for-cause mpMRI will also be captured. | At 24 months post-treatment | 
| Salvage-free survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Biochemical failure-free survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Histologic failure-free survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Metastasis-free survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Prostate cancer-specific survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | Up to 24 months | 
| Change in quality of life | Change from baseline in the EPIC questions 1-7 domains and in the visual analog score will be measured at baseline, 6, 12, 18, and 24 months using Scale Grade Group 1, 2, 3, and 4. | Baseline up to 24 months | 
| Change in patient-reported genitourinary function | Change from baseline in the EPIC questions 8-21 will be measured using Scale Grade Group 1, 2, 3, and 4. | Baseline up to 24 months |