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

• ClinicalTrials.gov Identifier: NCT01686958
• Recruitment Status: Completed
• First Posted: September 18, 2012
• Results First Posted: October 25, 2018
• Last Update Posted: February 11, 2020
• Sponsor: Profound Medical Inc.
• Information provided by (Responsible Party): Profound Medical Inc.

Tracking Information

• First Submitted Date: September 13, 2012
• First Posted Date: September 18, 2012
• Results First Submitted Date: August 28, 2018
• Results First Posted Date: October 25, 2018
• Last Update Posted Date: February 11, 2020
• Actual Study Start Date: March 13, 2013
• Actual Primary Completion Date: March 23, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 24, 2018)

• Safety - Evaluate the Frequency of Treatment Related Adverse Events [ Time Frame: 12 months from the Treatment Date ]
  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.
• Safety - Evaluate the Severity of Treatment Related Adverse Events [ Time Frame: 12 months from the Treatment Date ]
  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.

Original Primary Outcome Measures (submitted: September 13, 2012)

Evaluate the frequency and severity of device / treatment related adverse events associated with the use of the investigational system to coagulate prostate tissue. [ Time Frame: 6 months from the Treatment Date ]

Severity of adverse events per patient will be evaluated (from the treatment date to the 6 month follow-up date) and reported in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) standard published by the National Cancer Institute (NCI).

Current Secondary Outcome Measures (submitted: October 24, 2018)

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 [ Time Frame: On Treatment Date ]

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.

Original Secondary Outcome Measures (submitted: September 13, 2012)

Evaluate the effectiveness of the investigation system to thermally coagulate prostate tissue conforming to the target volume with a high degree of accuracy and precision. [ Time Frame: 6 months from the Treatment Date ]

• Conformal thermal coagulation of prostate tissue will be determined quantitatively using two measures of targeting accuracy: i. Dice Similarity Coefficient (DSC - unitless from 0 to 1), is a statistical validation metric to measure the degree of spatial overlap between two regions. ii. Over- and under-targeted volumes (outside the target volume ± ½ voxel margin), representing the amount of tissue ≥ target temperature (55°C) outside the target volume and < target temperature (55°C) inside the target volume, respectively. The over- and under-targeted volumes are expressed as a % of the target volume. • Coagulation of prostate tissue will be confirmed by measurement of the peripheral region of enhancement surrounding the Non-Perfused Volume (NPV) determined from Contrast-Enhanced MR images (CE-MRI) acquired immediately after treatment and at 6 months after treatment.

Current Other Pre-specified Outcome Measures (submitted: October 24, 2018)

• Treatment Efficacy - Biopsy [ Time Frame: 12 months from the Treatment Date ]
  Evaluate the effectiveness of the treatment to achieve disease control at 12 months based on biopsy results.
• Treatment Efficacy - PSA [ Time Frame: As per the Study Schedule, measured at 1-month, 3-months, 6-months and 12-months from the Treatment Date compared to Baseline ]
  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.
• Treatment Efficacy - Quality of Life - Urinary Symptoms [ Time Frame: Baseline and 12-months post Treatment ]
  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
• Treatment Efficacy - Quality of Life - Erectile Function [ Time Frame: Baseline and 12-months post Treatment ]
  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
• Treatment Efficacy - Quality of Life - Bowel Habits [ Time Frame: Baseline and 12-months post Treatment ]
  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

Original Other Pre-specified Outcome Measures (submitted: September 13, 2012)

In addition to patient safety and treatment feasibility, initial efficacy of using the investigation system to achieve adequate tumor control for their localized prostate cancer will also be evaluated. [ Time Frame: 6 months from the treatment date ]

• Evaluate the initial effectiveness of the treatment to achieve disease control at 6 months based on biopsy results.
• Characterize the pattern of PSA response in the first 6 months following treatment.
• Evaluate quality of life using the UCLA-PCI-SF & SF-12 v2, IPSS and IIEF standardized questionnaires in the first 6 months following treatment.

Descriptive Information

• Brief Title: Safety Study of MRI-guided Transurethral Ultrasound Ablation of Prostate Tissue to Treat Localized Prostate Cancer
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

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 Name: Prostate Ablation Device: PAD-105

Study Arms

Experimental: MR-Guided Transurethral US Ablation

MR-Guided Transurethral US Ablation of Prostate Tissue

Intervention: Device: MR-Guided Transurethral US Ablation of Prostate Tissue

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 13, 2012): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 11, 2019
• Actual Primary Completion Date: March 23, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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....

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 65 Years to 75 Years (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United States

Administrative Information

• NCT Number: NCT01686958
• Other Study ID Numbers: DOC-10246
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Profound Medical Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Profound Medical Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Profound Medical Inc.
• Verification Date: January 2020