Efficacy of Magnetic Resonance-guided High Intensity Focused Ultrasound for the Ablation of Breast Cancer: Correlation Between MRI and Histology. Single-Center, Single-Arm, Non-Randomized Trial
Phase: NA
Conditions: Breast Cancer, Invasive Ductal
Sponsor: Kantonsspital Winterthur KSW

 
 
MR guided HIFU for breast cancer, Version 1.1 of 31. August 2017 
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Clinical Investigation Plan 
EFFICACY OF MAGNETIC RESONANCE-GUIDED HIGH INTENSITY FOCUSED 
ULTRASOUND FOR THE ABLATION OF BREAST CANCER: CORRELATION BETWEEN 
MRI AND HISTOLOGY. 
Single-Center, Single-Arm, Non-Randomized Trial 
 (CE-aequivalent documentation) 
 
SHORT TITLE: MR guided HIFU for breast cancer 
 
 
Study Type: 
Intervention with Investigational Medical Device (IMD)  
Study Categorization: 
Clinical Trial with IMD Category C 
Study Registration: 
ClinicalTrials.gov Identifier: NCT03560102 
Registration number (from BAG portal):  
BASEC 2017-01282, SWISSMEDIC 2017-MD-0021 
Study Identifier: 
 
Sponsor-Investigator: 
Prof. Dr. med. Christoph A. Binkert 
Kantonsspital Winterthur 
Institut für Radiologie und Nuklearmedizin 
Brauerstrasse 15  
CH 8401 Winterthur  
Switzerland  
Phone: 0041 52 266 26 02 
E-Mail: christoph.binkert@ksw.ch 
Investigational Medical 
Device: 
Philips Sonalleve MR-HIFU Breast Therapy System 
Investigation plan Version 
and Date: 
Version 1.1, 31. August 2017 
 
 
CONFIDENTIAL 
The information contained in this document is confidential and the property of Institut für 
Radiologie und Nuklearmedizin, Kantonsspital Winterthur The information may not - in full or in 
part - be transmitted, reproduced, published, or disclosed to others than the applicable 
Independent Ethics Committee(s) and Competent Authority(ies) without prior written authorization 
from Institut für Radiologie und Nuklearmedizin, Kantonsspital Winterthur, except to the extent 
necessary to obtain informed consent from those participants who will participate in the study. 

 
MR guided HIFU for breast cancer, Version 1.1 of 31. August 2017 
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STUDY SYNOPSIS 
Sponsor / Sponsor-
Investigator 
Prof. Dr. med. Christoph A. Binkert 
Study Title: 
Efficacy of magnetic resonance-guided high intensity focused 
ultrasound for the ablation of breast cancer: correlation 
between MRI and histology. 
Short Title / Study ID: 
MR guided HIFU for breast cancer 
Investigation Plan Version 
and Date: 
Version V1.1 , 31. August 2017  
Trial registration: 
ClinicalTrials.gov Identifier: NCT 03560102 
Registration number (BAG portal):  
BASEC 2017-01282, SWISSMEDIC 2017-MD-0021 
Study category and 
Rationale 
Clinical study with IMD Category  C. 
Clinical Phase: 
Phase of development for medical device: 
Device is not CE or MD marked. 
Background and Rationale: 
The dedicated MR-HIFU unit has been shown to be safe and 
feasible to ablate breast tissue.  
The planned study should help to develop a minimal-invasive 
local therapy for breast cancer as an alternative treatment to 
surgery. 
Objective(s): 
The purpose of the study is to evaluate the efficacy of a 
dedicated MR-HIFU unit in ablating breast cancer with a non-
invasive method. 
Primary objective: to evaluate the accuracy of MRI as a 
non-invasive method for assessment of treatment success. 
Secondary objective: Evaluation of treatment efficacy. 
Outcome(s): 
Primary endpoint: accuracy of MRI as method for 
assessment of qualitative and quantitative treatment success 
compared to the results of the histopathological analysis 
performed as reference method. 
Secondary endpoint: evaluate treatment efficacy (necrosis 
of tumor and safety margin >1mm) 
Study design: 
Single-center, single-arm, non-randomized trial 

 
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Inclusion / Exclusion 
criteria: 
Key inclusion criteria: 
- 
Biopsy proven cT1-2 N0-2 MX invasive breast cancer with 
a size of ≤3.0cm. 
- 
Histological type of tumor: invasive ductal carcinoma 
(IDC) 
- 
Patient is scheduled for surgical resection of tumor at 
Kantonsspital Winterthur 
- 
Tumor location within the reach of the HIFU transducers 
with the patient in prone position; distance from skin and 
pectoral muscle to the tumor ≥ 1.0 cm. 
- 
Target breast fits in the cup of the dedicated MR-HIFU 
breast system 
- 
 
Key exclusion criteria: 
- 
neoadjuvant systemic therapy 
- 
prior radiotherapy in target breast 
- 
contraindications for study procedures 
- 
macro-calcifications in or around the targeted tumor 
- 
scar tissue or surgical clips in the direct path of the 
ultrasound beams 
- 
Women who are pregnant or breast feeding,  

 
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Measurements and 
procedures: 
Before treatment (Screening/Baseline): 
- 
Tumor assessment by MRI (routine procedure) 
- 
Location of tumor site 
- 
Check of inclusion/exclusion criteria 
- 
Medical history 
- 
Demographics, height, weight, WHO performance status 
- 
Baseline assessment of pain 
- 
Pregnancy test for women of child-bearing potential. 
 
Treatment (Study intervention): 
Evaluations before MR-HIFU treatment: 
- 
Physical examination of breast 
- 
Assessment of pain 
- 
Assessment of adverse events 
- 
Assessment of changes in concomitant therapy 
 
Evaluations during MR-HIFU treatment: 
- 
DCE-MRI after treatment 
- 
Documentation of treatment parameters 
- 
 
Evaluations before discharge of patient: 
- 
Physical examination of breast 
- 
Assessment of pain 
- 
Assessment of adverse events 
- 
Assessment of changes in concomitant therapy 
 
Follow-up (phone contact, day 2): 
- 
Assessment of pain. 
- 
Assessment of adverse events 
- 
Assessment of changes in concomitant therapy 
 
End of Study: 
- 
DCE-MRI 
- 
Physical examination of breast  
- 
Assessment of pain  
- 
Assessment of adverse events 
- 
Assessment of changes in concomitant therapy 
 
Surgery (non-study procedure): 
Surgical ablation of the tumor (histopathological analysis of 
tumor tissue). 

 
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Study Product / Intervention:  
Study product: 
Philips Sonalleve MR-HIFU Breast Therapy System 
Study intervention: 
The breast tumor lesion of qualified study patients will be 
treated with MR-HIFU under procedural sedation. Two follow-
up DCE-MRI scans will be performed for evaluation of 
treatment efficacy. The first DCE-MRI is done directly after 
the MR-HIFU treatment (patient still in sedation). 
Treatment time: 
- 
MR-HIFU procedure including preparation and first DCE-
MRI ( 2-3 hours) 
- 
Recovery time after procedure (ca. 3 hours). 
Follow-up MRI: 
The second DCE-MRI will be performed 8 (±2) days after 
treatment (ambulant procedure). 
Control Intervention (if 
applicable): 
not applicable  
Number of Participants with 
Rationale: 
This project is performed as a proof-of-concept study with a 
limited sample of 10 patients. 
Study Duration: 
Estimated duration of main investigational plan: 13 month 
(patient recruitment: 12 month; duration of individual patient 
participation 2-3 weeks) 
Study Schedule: 
First-Participant-In (planned): Q1/2018 
Last-Participant-Out (planned): Q2/2019 
Investigator(s): 
Prof. Dr. med. Christoph A. Binkert 
Kantonsspital Winterthur 
Institut für Radiologie und Nuklearmedizin 
Brauerstrasse 15  
CH 8401 Winterthur  
Switzerland  
Phone: 0041 52 266 26 02 
E-Mail: christoph.binkert@ksw.ch 
Study Centre(s): 
Single-center study 

 
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Statistical Considerations: 
This proof-of-concept study will be analyzed predominantly 
with methods of descriptive statistics. 
Primary outcome: 
Quantitative analysis: Comparison and correlation of results 
from histopathology and DCE-MRI regarding Size/Volume of 
tumor and volume/percentage of tumor necrosis 
 
Qualitative analysis: Comparison of results from 
histopathology and DCE-MRI regarding spatial congruence 
of ablated tumor tissue and width of margin 
 
Secondary outcome: 
Assessment of treatment efficacy (Effective treatment: 
complete necrosis of targeted tumor including safety margin 
(>1mm) 
 
Safety analysis 
AEs in general and additional predefined safety parameters 
will be presented by type and grade in tables showing 
frequency. 
 
Statement: 
This study will be conducted in compliance with the 
investigation plan, the current version of the Declaration of 
Helsinki, the ISO EN 14155 as well as all national legal and 
regulatory requirements.