Focal MR-Guided Focused Ultrasound Treatment of Localized Intermediate Risk Prostate Lesions

The hypothesis of this study is that focal treatment with ExAblate MRgFUS has the potential to be an effective non-invasive treatment for intermediate risk, organ-confined prostate lesions, with a low incidence of morbidity. The study hypothesis will be tested by measuring treatment-related safety and initial effectiveness parameters in the ExAblate MRgFUS treated patients, as described above.

Study Overview

• Status: Completed
• Conditions: Localized Intermediate Risk Prostate Lesions
• Intervention / Treatment: Device: ExAblate MR Guided Focused Ultrasound

Detailed Description

Objective of this pivotal trial is to assess safety and initial effectiveness of ExAblate MRgFUS in the treatment of intermediate risk, localized (organ confined) prostate lesions.

ExAblate treatment will be implemented as a focal lesion-selective therapy, directed at pre-defined volume(s)/sector(s) in the prostate, identified by mapping biopsy and multi-parametric MRI, rather than a whole gland or hemi-ablation treatment.

Safety: evaluate incidence and severity of adverse events associated with ExAblate's MRgFUS focal treatment of intermediate risk organ confined prostate lesions. The risk of ExAblate treatment-related incontinence and impotence will also be assessed in this study.

Effectiveness: determine the lesion control effect of ExAblate's MRgFUS focal treatment of intermediate risk organ-confined prostate lesions (confirmed by IMAGE-guided mapping biopsy results).

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Sperling Prostate Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Biopsy proven adenocarcinoma of the prostate (using a IMAGE-guided 14+ core mapping biopsy), and targeted cores as needed obtained up to 6 months prior to scheduled treatment
• Patient with intermediate risk, early-stage organ-confined prostate cancer (T1a up to T2b, N0, M0) and voluntarily chooses ExAblate thermal ablation as the non-invasive treatment, who may currently be on watchful waiting or active surveillance and not in need of imminent radical therapy.
• Patient with PSA less than or equal to 20 ng/mL
• Gleason score 7 (4 + 3 or 3 + 4), based on mapping prostate biopsy, with no more than 15mm cancer in maximal linear dimension in any single core
• Single hemilateral index Gleason 7 lesion, identified in the prostate based on biopsy mapping with supporting MRI; may have secondary Gleason 6 lesion on ipsilateral or contralateral side confirmed with biopsy and/or MRI

Exclusion Criteria

• Contraindications to MRI
• History of orchiectomy, PCa-specific chemotherapy, brachytherapy, cryotherapy, Photodynamic therapy or radical prostatectomy for treatment of prostate cancer; any prior radiation therapy to the pelvis for prostate cancer or any other malignancy
• Patient under medications that can affect PSA for the last 3 months prior to MRgFUS treatment (Androgen Deprivation Treatment; alpha reductase inhibitors)
• Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (approximately 3 hrs. sonication time)
• Any rectal pathology, anomaly or previous treatment, which could change acoustic properties of rectal wall or prevent safe probe insertion (e.g., stenosis, fibrosis, inflammatory bowel disease, etc.)
• Evidence of distant prostate cancer, i.e., including lymph nodes and/or metastasis of cancer on imaging
• Bladder cancer
• Urethral stricture/bladder neck contracture
• Prostatitis NIH categories I, II and III
• Implant near (<1 cm) the prostate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ExABlate MR Guided Focus Ultrasound; ExAblate MR Guided Focused Ultrasound - Local treatment of prostate lesions using Magnetic Resonance Imaging guided endorectally applied focused ultrasound energy.	Device: ExAblate MR Guided Focused Ultrasound; ExAblate MR Guided Focused Ultrasound - Local treatment of prostate lesions using Magnetic Resonance Imaging guided endorectally applied focused ultrasound energy.; Other Names: ExAblate 2100 Prostate System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Device and Procedure Related Adverse Events	The cumulative sum of adverse events was followed through Month 12 of the study.	12 months Post Treatment
Percentage of Subjects With NO Gleason Grade Group (GGG) Tissue in the Planned Region of Treatment (ROT) at 6 Months.	The first primary effectiveness endpoint is within area of treatment (Region of Treatment, ROT) prostate biopsy occurring at 6-months post-treatment. Positive biopsy was defined as any Gleason Grade Group (GGG) tissue identified within the area of planned Exablate ROT. Negative biopsy was defined No Gleason Grade Group (GGG) tissue within the area of planned ROT.	6 Months Post Treatment
Percentage of Subjects Showing a Reduction in PSA Value (Prostate Specific Antigen) From Baseline to 6-Months	The second primary effectiveness endpoint is the percentage of subjects experiencing a reduction in PSA value (Prostate Specific Antigen) from baseline to 6-months post-treatment. PSA values that increased or remained the same were considered an increase. Increased Prostate Specific Antigen levels in the blood is a common indication of prostate cancer. PSA results at 6 months - Value of ≤ 10ng/mL (Yes/No)	6-months Post Treatment
Percentage of Subjects With Non-Perfused Volume (NPV) Entirely Covered Target Gleason Grade Group (GGG) Tissue at Treatment.	The final primary effectiveness endpoint is percentage of subjects with NPV complete coverage of targeted Gleason tissue at treatment. NPV (non-perfused volume) is the volume of tissue ablated/treated, a measure of the completeness/effectiveness of the ablation.	6 Months Post Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate Specific Antigen (PSA)	Prostate Specific Antigen (PSA) concentration in the blood is commonly measured to screen for prostate cancer. Prostate Specific Antigen (PSA) was reported as a primary endpoint. Here it is presented to show levels at 6 Months and 12 Months post-treatment compared to Baseline (pre-treatment). Elevated PSA suggests potential cancer.	Baseline, 6 Months, 12 Months
Functional Assessment of Cancer Therapy - General (Fact-G) Total Score	The total FACT-G score ranges from 0 to 108 and is the summation of 4 subscale scores. The subscale scores are added to obtain the total score, which is calculated using a five-point scale from 0 (not at all) to 4 (very much). A higher FACT-G score indicates better overall well-being and quality of life. The FACT-G is an alternative scoring method to the Trial Outcome Index (TOI) which is also reported in this study.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.
Functional Assessment of Cancer Therapy - Prostate (Fact P) Total Score	The Fact-P Total Score (Score range: 0-156) is a comprehensive multidimensional quality of life measure designed specifically for patients with prostate cancer. It is a 39-item assessment in a 5-point (0-4) Likert-type Scale. Higher scores represent better symptomology, functioning and quality of life.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months
Functional Assessment of Cancer Therapy - Prostate (Fact-P) Trial Outcomes Index (TOI)	Functional Assessment of Cancer Therapy - P (Fact-P) Trial Outcomes Index (TOI, Score range: 1-104). An alternative scoring method to the Fact-G Total is the Trial Outcome Index (TOI), which is the sum of the Physical, Functional, and Lung Cancer Subscales. The TOI is reported to be an efficient and precise summary index of physical and functional outcomes. Higher scores indicate less symptomology and better physical and functional outcomes.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.
International Consultation on Incontinence Questionnaire (ICIQ-SF). Urinary Incontinence (ICIQ) Total Score	Urinary incontinence (ICIQ) Total Score (Score range: 0-21) is a simple questionnaire for evaluating the frequency, severity, and impact of urinary incontinence. High scores indicate greater impairment. Lower scores indicate better outcomes. This questionnaire assesses urinary incontinence and its impact on quality of life (QoL). So, a lower score implies less frequent and less severe incontinence, which is generally considered favorable.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.
International Prostate Symptom Score (IPSS Total Score)	High scores indicate worse symptomology. The total I-PSS score can range from 0 (asymptomatic) to 35 (very symptomatic). Additionally, there's a question about quality of life due to urinary symptoms, where patients rate their feelings from "delighted" to "terrible" regarding their current condition. This assessment helps clinicians understand the severity of BPH symptoms and guide treatment decisions.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.
International Prostate Symptom Score (IPSS) - Quality of Life Score	IPSS Urinary Symptoms (IPSS-QoL Score range: 0-5). Question 7 of the IPSS, the Quality-of-Life question, is "7. Nocturia: How many times do you typically get up at night to urinate? (Select from 0 to 5)." Zero (0) suggests no interference with sleep and 5 suggests greater interference with sleep. Thus, high scores indicate worse quality of life.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.
International Index of Erectile Function (IIEF-15) Erectile Dysfunction Overall Satisfaction	IIEF-15 Erectile Dysfunction Overall Satisfaction (IIEF-15 Overall Satisfaction range: 0-10). Low scores are worse.	Baseline, 3 Months, 6 Months, 9 Months, 12 Months.

Collaborators and Investigators

• Sponsor: InSightec
• Investigators: Principal Investigator: Behfar Ehdaie, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Ehdaie B, Tempany CM, Holland F, Sjoberg DD, Kibel AS, Trinh QD, Durack JC, Akin O, Vickers AJ, Scardino PT, Sperling D, Wong JYC, Yuh B, Woodrum DA, Mynderse LA, Raman SS, Pantuck AJ, Schiffman MH, McClure TD, Sonn GA, Ghanouni P. MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study. Lancet Oncol. 2022 Jul;23(7):910-918. doi: 10.1016/S1470-2045(22)00251-0. Epub 2022 Jun 14.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimated): August 6, 2012

Study Record Updates

• Last Update Posted (Actual): November 13, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Prostate cancer; Prostate; Non-invasive; MRgFUS; ExAblate; Gleason 7; InSightec; Intermediate Risk Prostate Lesions; Focal Prostate treatment
• Other Study ID Numbers: PCa003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO