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.

• Study Type: Interventional
• 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
• Enrollment: 30

Participant Flow

Recruitment Details
Pre-assignment Details

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 [1]
Not Completed	1
Reason Not Completed
Withdrawal by Subject	1
[1] No. of patients who completed ALL assessments at 12 months post treatment; 1 pt only had PSA test.

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 Number of Baseline Participants		30
Baseline Analysis Population Description		Baseline measures were only done for the patients who passed screening and eligibility criteria
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	2 6.7%
	>=65 years	28 93.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
	Female	0 0.0%
	Male	30 100.0%
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	30 participants
Multi-racial		1 3.3%
White/Caucasian		29 96.7%
		[1] Measure Description: Data was collected via a questionnaire completed by the patient at the Baseline Visit. Patients were asked to describe themselves by noting a "X" in one box only. Available options included; White/Caucasian; Black/African-American; Latino/Hispanic' Asian/Pacific Islander; Multi-Racial; Other.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	30 participants
Canada		12
United States		4
Germany		14
Subjects with erections sufficient for penetration at Baseline [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	30 participants
		21 70.0%
		[1] Measure Description: Erectile dysfunction was defined as a score of 0-1 for Question 2 of the International Index of Erectile Function (IIEF-15). Patients with erections sufficient for penetration had a score greater than or equal to 2.

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.
Overall Number of Participants Analyzed	30
Measure Type: Count of Participants; Unit of Measure: Participants
	30 100.0%

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.
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. 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.
Overall Number of Participants Analyzed	30
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: % of subjects
Hematuria - G1	43; (25 to 63)
Hematuria - G2	6.7; (0.8 to 22)
Urinary tract infection - G2	33; (17 to 53)
Epididymitis - G3	3.3; (0.1 to 17)
Urinary retention - G1	10; (2.1 to 27)
Urinary retention - G2	17; (5.6 to 35)
Obstructive micturition	10; (2.1 to 27)
Urinary incontinence - G1	3.3; (0.1 to 17)
Urinary incontinence - G2	10; (2.1 to 27)
Urinary stricture - G1	3.3; (0.1 to 17)
Urinary stricture - G2	3.3; (0.1 to 17)

3. 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.
Overall Number of Participants Analyzed	30
Mean (Standard Deviation); Unit of Measure: mm
Thermal ablation accuracy	0.1 (0.4)
Thermal ablation precision	1.3 (0.4)

4. 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.
Overall Number of Participants Analyzed	29
Measure Type: Count of Participants; Unit of Measure: Participants
Positive biopsy (clinically significant disease)	9 31.0%
Overall absence of clinically significant disease	20 69.0%

5. 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.
Overall Number of Participants Analyzed	30
Median (Inter-Quartile Range); Unit of Measure: ng/ml
PSA @ Baseline	5.8; (3.8 to 8.0)
PSA @ 1 month	0.8; (0.5 to 1.1)
PSA @ 3 months	0.9; (0.4 to 1.7)
PSA @ 6 months	0.8; (0.4 to 1.1)
PSA @ 12 months	0.8; (0.6 to 1.1)

6. 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.
Overall Number of Participants Analyzed		30
Median (Inter-Quartile Range); Unit of Measure: units on a scale
IPSS @ Baseline	Number Analyzed	30 participants
		8; (5 to 13)
IPSS @ 12 months	Number Analyzed	29 participants
		5; (4 to 7)

7. 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.
Overall Number of Participants Analyzed		30
Median (Inter-Quartile Range); Unit of Measure: units on a scale
IIEF-EF-15 @ Baseline	Number Analyzed	30 participants
		13; (6 to 28)
IIEF-EF-15 @ 12 months	Number Analyzed	29 participants
		13; (5 to 25)

8. 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.
Overall Number of Participants Analyzed		30
Median (Inter-Quartile Range); Unit of Measure: units on a scale
UCLA-PCI-SF-BH @ Baseline	Number Analyzed	30 participants
		100; (90 to 100)
UCLA-PCI-SF-BH @ 12 months	Number Analyzed	29 participants
		100; (100 to 100)

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 (%)
Total	--/--
Serious Adverse Events
	MR-Guided Transurethral US Ablation
	Affected / at Risk (%)
Total	2/30 (6.67%)
Infections and infestations
Epididymitis * [1]	1/30 (3.33%)
Renal and urinary disorders
Urinary retention * [2]	1/30 (3.33%)
* Indicates events were collected by non-systematic assessment; [1] Patient diagnosed with epididymitis on left side, requiring antibiotics. Shortly thereafter patient developed a fever requiring hospital admission with changes to prescribed antibiotics.; [2] After removal of suprapubic catheter (SPC) as per protocol, the patient experienced retention and received an urethral catheter, but he continued experiencing retention, hence was hospitalized & required a second SPC.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	MR-Guided Transurethral US Ablation
	Affected / at Risk (%)
Total	30/30 (100.00%)
Gastrointestinal disorders
Rectal pain *	1/30 (3.33%)
Fecal straining *	1/30 (3.33%)
Bloating *	3/30 (10.00%)
General disorders
Distended abdomen *	1/30 (3.33%)
Ear drainage *	1/30 (3.33%)
Fatigue *	1/30 (3.33%)
Hematoma or Ecchymosis: Buttock *	1/30 (3.33%)
Hemtoma or Ecchymosis: Femur *	1/30 (3.33%)
Hematoma or Ecchymosis: Sacral bone *	1/30 (3.33%)
Hyperkalemia *	1/30 (3.33%)
Patient movement at onset of treatment *	1/30 (3.33%)
Raised lump: Back *	1/30 (3.33%)
Sore throat *	1/30 (3.33%)
Pain: Back, hips, shoulder, upon catheter removal *	5/30 (16.67%)
Suprapubic Catheter: bleeding around SPC, urine leaking around SPC, blocked SPC, catheter fell out *	5/30 (16.67%)
Infections and infestations
Epididymitis *	1/30 (3.33%)
Fever *	1/30 (3.33%)
Renal and urinary disorders
Hematuria *	15/30 (50.00%)
Urinary tract infection *	10/30 (33.33%)
Urinary retention *	8/30 (26.67%)
Urinary incontinence *	4/30 (13.33%)
Urinary stricture *	2/30 (6.67%)
Bladder inflammation *	1/30 (3.33%)
Bladder irritability *	1/30 (3.33%)
Bladder spasm *	5/30 (16.67%)
Edema: penile and/or scrotal *	5/30 (16.67%)
Edema: testicular *	1/30 (3.33%)
Hemorrhagic cystitis *	1/30 (3.33%)
Increased post void urinary residual in bladder *	2/30 (6.67%)
Nocturia *	2/30 (6.67%)
Obstructive micturition *	3/30 (10.00%)
Penile discharge or bleeding *	10/30 (33.33%)
Prostate anatomical change or discoloration *	7/30 (23.33%)
Prostate inflammation *	1/30 (3.33%)
Prostate tissue sloughing *	1/30 (3.33%)
Scarred urethra *	1/30 (3.33%)
Urethral skin tags *	1/30 (3.33%)
Urinary frequency *	10/30 (33.33%)
Urinary hesitancy *	7/30 (23.33%)
Urinary sensation to void *	1/30 (3.33%)
Urinary urgency *	12/30 (40.00%)
Urine abnormality *	2/30 (6.67%)
Dysuria *	6/30 (20.00%)
Pain: Bladder, penile, perineal, prostate, urethral *	12/30 (40.00%)
Reproductive system and breast disorders
Erectile dysfunction or worsening erectile function *	11/30 (36.67%)
Ejaculation disorder *	7/30 (23.33%)
Hematospermia *	2/30 (6.67%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Mathieu Burtnyk
• Organization: Profound Medical
• Phone: 647-476-1350 ext 408
• EMail: mburtnyk@profoundmedical.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Profound Medical Inc.
• ClinicalTrials.gov Identifier: NCT01686958
• Other Study ID Numbers: DOC-10246
• First Submitted: September 13, 2012
• First Posted: September 18, 2012
• Results First Submitted: August 28, 2018
• Results First Posted: October 25, 2018
• Last Update Posted: February 11, 2020