Safety Study of MRI-guided Transurethral Ultrasound Ablation of Prostate Tissue to Treat Localized Prostate Cancer

Phase 1 Study: A Prospective, Multi-center, Single Arm Study - Evaluation of the Safety and Feasibility of MRI-guided Transurethral Ultrasound Therapy for the Ablation of Prostate Tissue in Patients With Localized Prostate Cancer

This study is to evaluate that the magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy system is safe and feasible to ablate prostate tissue in men with localized prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Device: MR-Guided Transurethral US Ablation of Prostate Tissue

Detailed Description

Profound Medical Inc. has developed a novel technology called the MRI-guided transurethral ultrasound therapy system. 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 completely within an 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, thereby reducing the risk of possible damage to important surrounding anatomy such as the rectum, urinary sphincters, neurovascular bundles and pelvic bone. This coagulation method, therefore, has the potential to have lower complication rates than conventional therapies.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Science Centre
• Germany
  • Heidelberg, Germany, 69120
    • German Cancer Research Center (DKFZ)
• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male, age ≥65
• Patient with low-risk, early-stage organ-confined prostate cancer (Stage T1c or T2a, N0, M0).
• Gleason score 6 (3+3)
• Prostate-specific antigen (PSA) ≤ 10 ng/ml
• Eligible for MR imaging (DOC-10252)

• Meets the following criteria on pre-treatment transrectal ultrasound imaging:

  1. No cysts or calcifications > 1.0 cm in size
  2. No evidence of extraprostatic extension or seminal vesicle invasion
  3. Overall prostate size less than 5 cm in sagittal length and less than 7 cm in diameter
• Biopsy confirmed adenocarcinoma of the prostate, performed at least 6 weeks prior to and no more than 6 months prior to the scheduled treatment.
• Eligible for General Anesthesia, as defined in American Society of Anesthesiologists (ASA)
• Normal rectal anatomy and rectal mucosa on digital rectal examination

Exclusion Criteria:

• Bleeding disorder
• Abnormal coagulation and current anticoagulant therapy.
• Acute or chronic Urinary Tract Infection
• Interest in future fertility
• History of allergy relevant medication or other
• History of any other malignancy other than skin cancer
• Patients with peripheral arterial disease with intermittent claudication or Leriches Syndrome
• Prior treatment of the prostate gland
• Prior treatment with 5 alpha reductase inhibitor allowed (not as prostate cancer treatment or prevention) as long as drug has been stopped for minimum 3 months
• History of any major rectal or pelvic surgery
• History of ulcerative colitis or other chronic inflammatory conditions affecting rectum
• History of documented clinical prostatitis requiring therapy within previous 6 months
• History of urethral and bladder outlet disorders, including urethral stricture disease, urethral diverticulae, bladder neck contracture, urethral fistulae which had required prior urethrotomy, urethral stenting, urethroplasty or chronic indwelling urethral catheter
• Patients with artificial urinary sphincter or any penile implant (metallic or non-metallic)
• Neurologic bladder disorders
• Untreated bladder stones
• History of acute urinary retention
• Confirmed or suspected bladder cancer
• Urinary sphincter abnormalities
• Active untreated gross hematuria for any cause
• Post Void Residual (PVR) bladder volume > 250 mL
• Obstructing median lobe enlarged out of proportion to the rest of the prostate and protruding significantly into the bladder

Additional exclusion criteria on file....

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MR-Guided Transurethral US Ablation; MR-Guided Transurethral US Ablation of Prostate Tissue	Device: MR-Guided Transurethral US Ablation of Prostate Tissue; The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is thermal coagulation of prostate tissue.; Other Names: Prostate Ablation Device: PAD-105

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Evaluate the Frequency of Treatment Related Adverse Events	All reported adverse events were recorded. The frequency was measured as the number of study participants who experienced a treatment/device related adverse event after receiving treatment delivery with PAD-105, the investigational device.	12 months from the Treatment Date
Safety - Evaluate the Severity of Treatment Related Adverse Events	Severity of treatment/device related adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) standard (version 4), published by the National Cancer Institute (NCI). There was no intraoperative complication, no rectal injury or fistula and no severe urinary incontinence. No Grade 4 (G4) or higher adverse events and only one attributable Grade 3 (G3) event; reported below. The common and significant Grade 1 (G1) and Grade 2 (G2) genitourinary events have also been reported.	12 months from the Treatment Date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Evaluate the Effectiveness of the Investigational System to Thermally Coagulate Prostate Tissue Conforming to the Target Volume With a High Degree of Accuracy and Precision	Conformal thermal coagulation of prostate tissue will be determined quantitatively using measures of targeting accuracy which compare the spatial difference between the target volume and target temperature isotherm determined from MR thermometry images acquired during treatment.	On Treatment Date

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Efficacy - Biopsy	Evaluate the effectiveness of the treatment to achieve disease control at 12 months based on biopsy results.	12 months from the Treatment Date
Treatment Efficacy - PSA	Based on measurements obtained at each study visit, characterize the pattern of PSA response within the first 12 months following treatment in comparison to baseline.	As per the Study Schedule, measured at 1-month, 3-months, 6-months and 12-months from the Treatment Date compared to Baseline
Treatment Efficacy - Quality of Life - Urinary Symptoms	Evaluate quality of life in the first 12 months following Treatment compared to Baseline, using a standardized questionnaire, International Prostate Symptom Score (IPSS), which focuses on urinary symptoms. Total Score: 0 - 35 0-7 - mildly symptomatic 8-19 - moderately symptomatic 20-35 - severely symptomatic	Baseline and 12-months post Treatment
Treatment Efficacy - Quality of Life - Erectile Function	Evaluate quality of life in the first 12 months following Treatment compared to Baseline, using a standardized questionnaire, Erectile Function EF domain of the International Index of Erectile Function (IIEF-15), which focuses on erectile symptoms. Minimum score value - 0 Maximum score value - 30 A higher score corresponds to a better outcome; lower score indicative of erectile dysfunction	Baseline and 12-months post Treatment
Treatment Efficacy - Quality of Life - Bowel Habits	Evaluate quality of life in the first 12 months following Treatment compared to Baseline, using a standardized questionnaire, Bowel Habits domain of the UCLA Prostate Cancer Index Short Form (UCLA-PCl-SF-BH), which focuses on bowel symptoms. Minimum score value - 0 Maximum score value - 100 A higher score corresponds to better outcome	Baseline and 12-months post Treatment

Collaborators and Investigators

• Sponsor: Profound Medical Inc.
• Investigators: Principal Investigator: Joseph Chin, MD, London Health Science Center; Principal Investigator: James Relle, MD, William Beaumont Hospitals; Principal Investigator: Ryan Berglund, MD, The Cleveland Clinic; Principal Investigator: Heinz P Schlemmer, MD, German Cancer Research Center

Publications and helpful links

General Publications

• Chin JL, Billia M, Relle J, Roethke MC, Popeneciu IV, Kuru TH, Hatiboglu G, Mueller-Wolf MB, Motsch J, Romagnoli C, Kassam Z, Harle CC, Hafron J, Nandalur KR, Chronik BA, Burtnyk M, Schlemmer HP, Pahernik S. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial. Eur Urol. 2016 Sep;70(3):447-55. doi: 10.1016/j.eururo.2015.12.029. Epub 2016 Jan 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 13, 2013
• Primary Completion (ACTUAL): March 23, 2015
• Study Completion (ACTUAL): June 11, 2019

Study Registration Dates

• First Submitted: September 13, 2012
• First Submitted That Met QC Criteria: September 13, 2012
• First Posted (ESTIMATE): September 18, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Prostate Cancer; Minimally invasive; MRI-guided; High intensity transurethral ultrasound ablation; Real-time temperature feedback control
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: DOC-10246