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

• Sponsor: Profound Medical Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01686958
• Collaborator: (none)
• Enrollment: 30
• Locations: 3
• Arm: 1
• Actual Duration (Months): 74.9
• Patients Per Site: 10
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Device: MR-Guided Transurethral US Ablation of Prostate Tissue	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 13, 2013
• Actual Primary Completion Date: Mar 23, 2015
• Actual Study Completion Date: Jun 11, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety - Evaluate the Frequency of Treatment Related Adverse Events [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.

2. Safety - Evaluate the Severity of Treatment Related Adverse Events [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.

Secondary Outcome Measures

1. 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 [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.

Other Outcome Measures

1. Treatment Efficacy - Biopsy [12 months from the Treatment Date]

   Evaluate the effectiveness of the treatment to achieve disease control at 12 months based on biopsy results.

2. Treatment Efficacy - PSA [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.

3. Treatment Efficacy - Quality of Life - Urinary Symptoms [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

4. Treatment Efficacy - Quality of Life - Erectile Function [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

5. Treatment Efficacy - Quality of Life - Bowel Habits [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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....

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
2	London Health Science Centre	London	Ontario	Canada	N6A 5W9
3	German Cancer Research Center (DKFZ)	Heidelberg		Germany	69120

Sponsors and Collaborators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Profound Medical Inc.
• ClinicalTrials.gov Identifier: NCT01686958
• Other Study ID Numbers: DOC-10246
• First Posted: Sep 18, 2012
• Last Update Posted: Feb 11, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Profound Medical Inc.: Prostate Cancer; High intensity transurethral ultrasound ablation; MRI-guided; Minimally invasive; Real-time temperature feedback control
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	Technology developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Study is a prospective, multi-center, single arm trial conducted in US, Canada and Europe. All subjects received the same treatment. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	MR-Guided Transurethral US Ablation
Arm/Group Description	MR-Guided Transurethral US Ablation of Prostate Tissue 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 prescribed prostate tissue.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 6.7%
>=65 years	28 93.3%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	30 100%
Race/Ethnicity, Customized (Count of Participants)
Multi-racial	1 3.3%
White/Caucasian	29 96.7%
Region of Enrollment (participants) [Number]
Canada	12 40%
United States	4 13.3%
Germany	14 46.7%
Subjects with erections sufficient for penetration at Baseline (Count of Participants)
Count of Participants [Participants]	21 70%

Outcome Measures

1. Primary Outcome

Title	Safety - Evaluate the Frequency of Treatment Related Adverse Events
Description	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.
Time Frame	12 months from the Treatment Date

Outcome Measure Data

Analysis Population Description

The safety population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
Count of Participants [Participants]	30 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
	Comments	A total of 30 subjects will be accrued to this study and treated with the PAD-105. The sample size is based primarily on feasibility and logistical concerns, however, is sufficiently large to allow the safety objectives to be met. Specifically, with 30 total patients, if no treatment-related grade 4 or 5 adverse events are observed, then a one-sided, 95% confidence interval would have an upper bound of 0.095.
	Type of Statistical Test	Other
	Comments	This is a primarily descriptive study, no statistical analysis is planned; however, analyses were performed at the alpha=0.05 level of significance and exact analyses will be used wherever possible.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		For continuous outcomes, standard summary statistics will include n, mean, standard deviation, median, minimum and maximum. For categorical data, tables will show n and % of patients.

2. Secondary Outcome

Title	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
Description	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.
Time Frame	On Treatment Date

Outcome Measure Data

Analysis Population Description

The analysis population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
Thermal ablation accuracy	0.1 (0.4)
Thermal ablation precision	1.3 (0.4)

3. Other Pre-specified Outcome

Title	Treatment Efficacy - Biopsy
Description	Evaluate the effectiveness of the treatment to achieve disease control at 12 months based on biopsy results.
Time Frame	12 months from the Treatment Date

Outcome Measure Data

Analysis Population Description

One patient did not complete the 12-month visit, therefore 29 patients were included in this analysis.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	29
Positive biopsy (clinically significant disease)	9 30%
Overall absence of clinically significant disease	20 66.7%

4. Other Pre-specified Outcome

Title	Treatment Efficacy - PSA
Description	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.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
PSA @ Baseline	5.8
PSA @ 1 month	0.8
PSA @ 3 months	0.9
PSA @ 6 months	0.8
PSA @ 12 months	0.8

5. Other Pre-specified Outcome

Title	Treatment Efficacy - Quality of Life - Urinary Symptoms
Description	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
Time Frame	Baseline and 12-months post Treatment

Outcome Measure Data

Analysis Population Description

One patient did not complete the 12-month visit questionnaire in its entirety, hence overall number of patients analyzed is 29 versus 30 at baseline.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
IPSS @ Baseline	8
IPSS @ 12 months	5

6. Other Pre-specified Outcome

Title	Treatment Efficacy - Quality of Life - Erectile Function
Description	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
Time Frame	Baseline and 12-months post Treatment

Outcome Measure Data

Analysis Population Description

One patient did not complete the 12-month visit questionnaire in its entirety, hence overall number of patients analyzed is 29 versus 30 at baseline.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
IIEF-EF-15 @ Baseline	13
IIEF-EF-15 @ 12 months	13

7. Other Pre-specified Outcome

Title	Treatment Efficacy - Quality of Life - Bowel Habits
Description	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
Time Frame	Baseline and 12-months post Treatment

Outcome Measure Data

Analysis Population Description

One patient did not complete the 12-month visit questionnaire in its entirety, hence overall number of patients analyzed is 29 versus 30 at baseline.

Arm/Group Title	MR-Guided Transurethral Ultrasound of Prostate Tissue Ablation
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
UCLA-PCI-SF-BH @ Baseline	100
UCLA-PCI-SF-BH @ 12 months	100

8. Primary Outcome

Title	Safety - Evaluate the Severity of Treatment Related Adverse Events
Description	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.
Time Frame	12 months from the Treatment Date

Outcome Measure Data

Analysis Population Description

The safety population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.

Arm/Group Title	MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue
Arm/Group Description	The technology is developed to treat patients with organ confined prostate cancer. The therapeutic endpoint of this technology is whole gland ablation. Treatment delivery using an investigational medical device, PAD-105, a MRI-guided transurethral ultrasound whole gland prostate ablation.
Measure Participants	30
Hematuria - G1	43
Hematuria - G2	6.7
Urinary tract infection - G2	33
Epididymitis - G3	3.3
Urinary retention - G1	10
Urinary retention - G2	17
Obstructive micturition	10
Urinary incontinence - G1	3.3
Urinary incontinence - G2	10
Urinary stricture - G1	3.3
Urinary stricture - G2	3.3

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	Adverse events were assessed and documented at each follow-up visit. The severity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) standard published by the National Cancer Institute (NCI).
Arm/Group Title	MR-Guided Transurethral US Ablation
Arm/Group Description	MR-Guided Transurethral US Ablation of Prostate Tissue 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 prescribed prostate tissue.
All Cause Mortality
	MR-Guided Transurethral US Ablation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MR-Guided Transurethral US Ablation
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Infections and infestations
Epididymitis	1/30 (3.3%)
Renal and urinary disorders
Urinary retention	1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	MR-Guided Transurethral US Ablation
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Gastrointestinal disorders
Rectal pain	1/30 (3.3%)
Fecal straining	1/30 (3.3%)
Bloating	3/30 (10%)
General disorders
Distended abdomen	1/30 (3.3%)
Ear drainage	1/30 (3.3%)
Fatigue	1/30 (3.3%)
Hematoma or Ecchymosis: Buttock	1/30 (3.3%)
Hemtoma or Ecchymosis: Femur	1/30 (3.3%)
Hematoma or Ecchymosis: Sacral bone	1/30 (3.3%)
Hyperkalemia	1/30 (3.3%)
Patient movement at onset of treatment	1/30 (3.3%)
Raised lump: Back	1/30 (3.3%)
Sore throat	1/30 (3.3%)
Pain: Back, hips, shoulder, upon catheter removal	5/30 (16.7%)
Suprapubic Catheter: bleeding around SPC, urine leaking around SPC, blocked SPC, catheter fell out	5/30 (16.7%)
Infections and infestations
Epididymitis	1/30 (3.3%)
Fever	1/30 (3.3%)
Renal and urinary disorders
Hematuria	15/30 (50%)
Urinary tract infection	10/30 (33.3%)
Urinary retention	8/30 (26.7%)
Urinary incontinence	4/30 (13.3%)
Urinary stricture	2/30 (6.7%)
Bladder inflammation	1/30 (3.3%)
Bladder irritability	1/30 (3.3%)
Bladder spasm	5/30 (16.7%)
Edema: penile and/or scrotal	5/30 (16.7%)
Edema: testicular	1/30 (3.3%)
Hemorrhagic cystitis	1/30 (3.3%)
Increased post void urinary residual in bladder	2/30 (6.7%)
Nocturia	2/30 (6.7%)
Obstructive micturition	3/30 (10%)
Penile discharge or bleeding	10/30 (33.3%)
Prostate anatomical change or discoloration	7/30 (23.3%)
Prostate inflammation	1/30 (3.3%)
Prostate tissue sloughing	1/30 (3.3%)
Scarred urethra	1/30 (3.3%)
Urethral skin tags	1/30 (3.3%)
Urinary frequency	10/30 (33.3%)
Urinary hesitancy	7/30 (23.3%)
Urinary sensation to void	1/30 (3.3%)
Urinary urgency	12/30 (40%)
Urine abnormality	2/30 (6.7%)
Dysuria	6/30 (20%)
Pain: Bladder, penile, perineal, prostate, urethral	12/30 (40%)
Reproductive system and breast disorders
Erectile dysfunction or worsening erectile function	11/30 (36.7%)
Ejaculation disorder	7/30 (23.3%)
Hematospermia	2/30 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor will review the publication text within twenty days of receipt, however, Sponsor can request changes if text contains Sponsor's Confidential Information, or text contains information for which the Sponsor wishes to obtain patent protection, whereupon such information will be removed or there will be a delay to the presentation or publication to enable the Sponsor to proceed with patent application for an additional 60 days or until patent application has been filed, whichever is earlier.