Prostate Cancer
Conditions
Keywords
Prostate Cancer, High intensity transurethral ultrasound ablation, MRI-guided, Minimally invasive, Real-time temperature feedback control
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.
Interventions
DEVICEMR-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.
Sponsors
Profound Medical Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
65 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
| 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. |
| 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 |
Countries
Canada, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MR-Guided Transurethral US Ablation 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. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MR-Guided Transurethral US Ablation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 28 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race/Ethnicity, Customized Multi-racial | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 29 Participants |
| Region of Enrollment Canada | 12 participants |
| Region of Enrollment Germany | 14 participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 30 Participants |
| Subjects with erections sufficient for penetration at Baseline | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
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.
Time frame: 12 months from the Treatment Date
Population: The safety population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Frequency of Treatment Related Adverse Events | 30 Participants |
Comparison: 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.
Primary
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.
Time frame: 12 months from the Treatment Date
Population: The safety population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Hematuria - G1 | 43 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Hematuria - G2 | 6.7 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Epididymitis - G3 | 3.3 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary retention - G1 | 10 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Obstructive micturition | 10 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary incontinence - G1 | 3.3 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary stricture - G2 | 3.3 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary tract infection - G2 | 33 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary retention - G2 | 17 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary incontinence - G2 | 10 % of subjects |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Safety - Evaluate the Severity of Treatment Related Adverse Events | Urinary stricture - G1 | 3.3 % of subjects |
Secondary
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.
Time frame: On Treatment Date
Population: The analysis population consists of all subjects who underwent treatment delivery with PAD-105, the investigational medical device.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | 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 | Thermal ablation accuracy | 0.1 mm | Standard Deviation 0.4 |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | 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 | Thermal ablation precision | 1.3 mm | Standard Deviation 0.4 |
Other Pre-specified
Treatment Efficacy - Biopsy
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
Population: One patient did not complete the 12-month visit, therefore 29 patients were included in this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Biopsy | Positive biopsy (clinically significant disease) | 9 Participants |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Biopsy | Overall absence of clinically significant disease | 20 Participants |
Other Pre-specified
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.
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - PSA | PSA @ Baseline | 5.8 ng/ml |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - PSA | PSA @ 1 month | 0.8 ng/ml |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - PSA | PSA @ 3 months | 0.9 ng/ml |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - PSA | PSA @ 6 months | 0.8 ng/ml |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - PSA | PSA @ 12 months | 0.8 ng/ml |
Other Pre-specified
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
Time frame: Baseline and 12-months post Treatment
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Bowel Habits | UCLA-PCI-SF-BH @ Baseline | 100 units on a scale |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Bowel Habits | UCLA-PCI-SF-BH @ 12 months | 100 units on a scale |
Other Pre-specified
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
Time frame: Baseline and 12-months post Treatment
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Erectile Function | IIEF-EF-15 @ Baseline | 13 units on a scale |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Erectile Function | IIEF-EF-15 @ 12 months | 13 units on a scale |
Other Pre-specified
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
Time frame: Baseline and 12-months post Treatment
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Urinary Symptoms | IPSS @ Baseline | 8 units on a scale |
| MR-Guided Transurethral Ultrasound Ablation of Prostate Tissue | Treatment Efficacy - Quality of Life - Urinary Symptoms | IPSS @ 12 months | 5 units on a scale |