Clinical trial NCT02766543: Pivotal Study of MRI-guided Transurethral Ultrasound Ablation in Patients With Localized Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: prostate cancer
high intensity transurethral ultrasound ablation
MRI-guided
minimally invasive
real-time temperature feedback control
whole-gland
TULSA
Lead sponsor: Profound Medical Inc.
Sponsor class: OTHER
First posted: 2016-05-09
Enrollment: 150
Sex: MALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety Endpoint - Incidence of treatment-emergent adverse events
timeFrame: 1 year
measure: Efficacy Endpoint - Proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value.
timeFrame: 1 year
Secondary outcomes:
measure: Erectile Dysfunction Endpoint
timeFrame: 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).
measure: Erection Firmness Endpoint
timeFrame: 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).
measure: Urinary Incontinence Endpoint
timeFrame: 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).
measure: PSA Nadir Endpoint
timeFrame: 1 year
measure: PSA Stability Endpoint
timeFrame: 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).
measure: Prostate Volume Endpoint
timeFrame: 1 year
measure: Prostate Biopsy Endpoint
timeFrame: 1 year
measure: IPSS Endpoint
timeFrame: 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).
measure: IIEF Endpoint
timeFrame: 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).
measure: EPIC Endpoint
timeFrame: 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).
measure: Targeting Accuracy Endpoint
timeFrame: During treatment
measure: CE-MRI Endpoint
timeFrame: Immediately after treatment
measure: mpMRI Endpoint
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale Cancer Centre
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Medicine
state: Maryland
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Cologne
country: Germany
facility: University Hospital of Cologne
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg (University of Heidelberg, Dept of Urology)
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Barcelona
country: Spain
facility: ResoFus Alomar (Hospital Universitari De Bellvitge)
Study officials:
affiliation: University of Chicago
name: Scott Eggener, MD
role: PRINCIPAL_INVESTIGATOR
References: