Prostate Cancer
Conditions
Keywords
prostate cancer, high intensity transurethral ultrasound ablation, MRI-guided, minimally invasive, real-time temperature feedback control, whole-gland, TULSA
Brief summary
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
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.
Interventions
Magnetic resonance imaging-guided transurethral ultrasound ablation is a novel minimally-invasive procedure where the therapeutic endpoint is prostate ablation through thermal coagulation.
Sponsors
Profound Medical Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
MALE
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male, age 45 to 80 years 2. 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). 3. 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
1. Evidence (including Baseline MRI and bone scan) of extracapsular extension, sphincter involvement, seminal vesicle invasion, lymph node invasion or metastases 2. Suspected tumour on Baseline MRI within 3 mm of the prostatic urethra, or in the prostate apex within 3 mm from the sphincter plane 3. Prior definitive treatment of prostate cancer 4. Prior transurethral resection of the prostate (TURP) 5. 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. 6. Prostate calcifications \> 1 cm in largest diameter, on Baseline Ultrasound 7. Cysts \> 1 cm in largest diameter, on Baseline MRI 8. Bleeding disorder (INR \> ULN and PTT \> ULN) 9. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Endpoint - Incidence of treatment-emergent adverse events | 1 year | 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). |
| Efficacy Endpoint - Proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. | 1 year | Prostate ablation efficacy will be evaluated using the proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Incontinence Endpoint | 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). | 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). |
| PSA Nadir Endpoint | 1 year | Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml. |
| PSA Stability Endpoint | 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). | Proportion of patients with PSA ≤ 0.5 ng/ml at the most recent follow-up visit. |
| Prostate Volume Endpoint | 1 year | Prostate volume reduction, evaluated on MRI between the treatment day and 12-month follow-up visits. |
| Prostate Biopsy Endpoint | 1 year | Proportion of patients with negative prostate biopsy at the 12-month follow-up visit, determined by transrectal ultrasound-guided 10-core biopsy. |
| Erectile Dysfunction Endpoint | 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). | Rate of erectile dysfunction, determined by the change from baseline of the proportion of patients with IIEF-5 \< 17. |
| IIEF Endpoint | 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). | 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. |
| EPIC Endpoint | 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). | 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. |
| Targeting Accuracy Endpoint | During treatment | 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). |
| CE-MRI Endpoint | Immediately after treatment | 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. |
| mpMRI Endpoint | 1 year | 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. |
| IPSS Endpoint | 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). | Change in International Prostate Symptom Score (IPSS), between the baseline and most recent follow-up visit. |
| Erection Firmness Endpoint | 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). | Rate of erection firmness sufficient for penetration, determined by the change from baseline of the proportion of patients with IIEF item 2 ≥ 2. |
Countries
Canada, Germany, Netherlands, Spain, United States
Outcome results
None listed