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

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

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.

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.

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