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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02766543
Recruitment Status : Active, not recruiting
First Posted : May 9, 2016
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Profound Medical Inc.

Tracking Information
First Submitted Date  ICMJE May 5, 2016
First Posted Date  ICMJE May 9, 2016
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE September 21, 2016
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2018)
  • Safety Endpoint - Incidence of treatment-emergent adverse events [ Time Frame: 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. [ Time Frame: 1 year ]
    Prostate ablation efficacy will be evaluated using the proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value.
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
Incidence of treatment-emergent adverse events [ Time Frame: 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).
Change History Complete list of historical versions of study NCT02766543 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2018)
  • Erectile Dysfunction Endpoint [ Time Frame: 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.
  • Erection Firmness Endpoint [ Time Frame: 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.
  • Urinary Incontinence Endpoint [ Time Frame: 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 [ Time Frame: 1 year ]
    Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml.
  • PSA Stability Endpoint [ Time Frame: 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 [ Time Frame: 1 year ]
    Prostate volume reduction, evaluated on MRI between the treatment day and 12-month follow-up visits.
  • Prostate Biopsy Endpoint [ Time Frame: 1 year ]
    Proportion of patients with negative prostate biopsy at the 12-month follow-up visit, determined by transrectal ultrasound-guided 10-core biopsy.
  • IPSS Endpoint [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2016)
Proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. [ Time Frame: 1 year ]
Prostate ablation efficacy will be evaluated using the proportion of patients achieving a PSA nadir ≤ 25% of the pre-treatment baseline value.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 6, 2016)
  • Rate of erectile dysfunction through Quality of Life questionnaire [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Rate of erection firmness through Quality of Life questionnaire [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Rate of urinary incontinence through Quality of Life questionnaire [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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).
  • Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml [ Time Frame: 1 year ]
    Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml.
  • Proportion of patients with stable PSA levels [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Level of prostate reduction [ Time Frame: 1 year ]
    Prostate volume reduction, evaluated on MRI between the treatment day and 12-month follow-up visits.
  • Proportion of patients with negative biopsy [ Time Frame: 1 year ]
    Proportion of patients with negative prostate biopsy at the 12-month follow-up visit, determined by transrectal ultrasound-guided 10-core biopsy.
  • Change in international prostate symptom score using a Quality of Life questionnaire. [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Change in erectile and orgasmic function, sexual desire and intercourse satisfaction using a Quality of Life questionnaire. [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Change in urinary, bowel, sexual and hormonal domains using a Quality of Life questionnaire. [ Time Frame: At each visit post treatment throughout the total study follow-up - (1 month, 3 months, 6 months, 1 year, 1.5 years, 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.
  • Qualitative assessment of prostate ablation through visualization from MRI [ Time Frame: 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.
  • Characterization of the effect of the transurethral ultrasound ablation device from MRI data values [ Time Frame: 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.
 
Descriptive Information
Brief Title  ICMJE Pivotal Study of MRI-guided Transurethral Ultrasound Ablation in Patients With Localized Prostate Cancer
Official Title  ICMJE 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
Brief Summary A prospective, multi-center, single-arm study, planned in 110 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Device: MRI-guided Transurethral Ultrasound Ablation
Magnetic resonance imaging-guided transurethral ultrasound ablation is a novel minimally-invasive procedure where the therapeutic endpoint is prostate ablation through thermal coagulation.
Other Name: TULSA-PRO
Study Arms  ICMJE Experimental: MRI-guided Transurethral Ultrasound Ablation Device
Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue.
Intervention: Device: MRI-guided Transurethral Ultrasound Ablation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 8, 2018)
115
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2016)
110
Estimated Study Completion Date  ICMJE February 2023
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  3. Clinical stage ≤ T2b
  4. Gleason score ≤ 3 + 4
  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

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 45 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02766543
Other Study ID Numbers  ICMJE GCP-10100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Profound Medical Inc.
Study Sponsor  ICMJE Profound Medical Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott Eggener, MD University of Chicago
PRS Account Profound Medical Inc.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP