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

Not Applicable

Active, not recruiting

• Conditions: Prostate Cancer
• Interventions: Device: MRI-guided Transurethral Ultrasound Ablation

• Registration Number: NCT02766543
• Lead Sponsor: Profound Medical Inc.

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.

Study Timeline

• Study First Submitted: 2016-05-05
• Study First Submitted QC: 2016-05-06
• Study First Posted: 2016-05-09
• Study Start: 2016-09-21
• Status Verified: 2023-11
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-22
• Primary Completion: 2024-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 150

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 exclusion criteria.

10. Acute unresolved Urinary Tract Infection (UTI)

11. Interest in future fertility

12. 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.

13. Patients with peripheral arterial disease with intermittent claudication or Leriches Syndrome

14. Patients with diabetes who have evidence of complications from their diabetes, such as end organ sequelae of diabetes or Hemoglobin A1c > 7%.

15. History of any major rectal or pelvic surgery or radiotherapy

16. History of ulcerative colitis or other chronic inflammatory conditions affecting rectum (includes rectal fistula, anal stenosis)

17. Documented clinical prostatitis requiring therapy within 6 months prior to Treatment

18. 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

19. Patients with artificial urinary sphincter or any penile implant

20. Severe neurogenic bladder

21. Untreated bladder stones

22. History of acute urinary retention within the last 12 months

23. Active untreated gross hematuria for any cause

24. Post Void Residual (PVR) bladder volume > 250 mL

25. 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

26. Any prostate related investigational therapy within 6 months of Visit 1

27. History of Parkinson's disease or multiple sclerosis

28. History of drug abuse

29. Known infectious disease including HIV positivity or AIDS-related illness, HBV and HCV

30. Current unilateral or bilateral hydronephrosis

31. Allergy or contraindications to administration of the GI anti-spasmodic drug:

    1. Patients in the USA: Glucagon
    2. Patients in Canada and Europe: Buscopan (Hyoscine)

32. 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

33. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MRI-guided Transurethral Ultrasound Ablation Device	MRI-guided Transurethral Ultrasound Ablation	Magnetic resonance imaging-guided transurethral ultrasound ablation of whole-gland prostate tissue.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
Prostate Volume Endpoint	1 year	Prostate volume reduction, evaluated on MRI between the treatment day and 12-month follow-up visits.
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.
PSA Nadir Endpoint	1 year	Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml.
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.
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.
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).
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 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 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.

Trial Locations

Locations (14)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Yale Cancer Centre; 🇺🇸 New Haven, Connecticut, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

William Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

Johns Hopkins Medicine; 🇺🇸 Baltimore, Maryland, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

University Hospital of Cologne; 🇩🇪 Cologne, Germany

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

Universitätsklinikum Heidelberg (University of Heidelberg, Dept of Urology); 🇩🇪 Heidelberg, Germany

ResoFus Alomar (Hospital Universitari De Bellvitge); 🇪🇸 Barcelona, Spain