Efficacy of MR-HIFU Ablation of Breast Cancer

Efficacy of Magnetic Resonance-guided High Intensity Focused Ultrasound for the Ablation of Breast Cancer

This study evaluates the efficacy of MR-HIFU ablation of breast cancer. Ten patients with early-stage breast cancer with a maximum diameter of 3 cm will undergo MR-HIFU ablation, followed by MRI and surgical resection to evaluate treatment effect. The main purpose of the study is to demonstrate the feasibility of total tumor ablation with MR-HIFU. The secondary objective is safety assessment.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Philips Sonalleve MR-HIFU Breast Tumor Therapy System

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manon NG Braat, MD; Phone Number: :+3188-7574881; Email: M.N.G.Braat-3@umcutrecht.nl
• Study Contact Backup: Name: Josanne S de Maar, MD; Phone Number: +3188-7563142; Email: j.s.demaar@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women, aged 18 years and older.
• Able to give informed consent herself.
• World Health Organization (WHO) performance score ≤ 2.
• Biopsy proven cT1-2 N0-2 MX invasive breast cancer with a size of ≤ 3.0 cm.
• Histological type of tumor: invasive ductal carcinoma (IDC), not otherwise specified (NOS) or no special type (NST).
• The target breast fits in the cup of the dedicated MR-HIFU breast system.
• Patient weight is limited to ≤ 90 kg, because of restrictions to the HIFU table top.

Additional inclusion criteria based on DCE-MRI findings:

• The distance of the tumor, including a 5 mm margin around the tumor, from the skin, nipple and pectoral wall is at least 1.0 cm measured on MRI.
• The tumor is located within the reach of the HIFU beam produced by the transducers in the HIFU breast system.

Exclusion Criteria:

• Prior treatment with: neo-adjuvant systemic therapy in the past 3 months or radiotherapy or thermal therapy or surgery of any kind in the targeted breast.
• Contraindications to MR imaging according to the hospital guidelines (e.g. pacemaker in situ, severe claustrophobia, big metal implants, body size incompatible with MR bore).
• Contraindications to administration of gadolinium-based contrast agent, including: prior allergic reaction to a gadolinium-based contrast agent, kidney disease (e.g. nephrogenic systemic fibrosis, nephrogenic fibrosing dermopathy) and/or renal failure (GFR < 30 ml/min/1,73m2).
• Contra-indications for procedural sedation analgesia with Propofol and Esketamine or Propofol and Remifentanil.
• Extensive intraductal components in the lesion determined by biopsy.
• Scar tissue or surgical clips in the HIFU beam path.
• Inability to lie in prone position.
• Pregnancy or lactation.
• Communication barrier with patient.

The following groups of patients will be excluded because the risk of adjuvant over- or undertreatment due to performing the Bloom and Richardson (B&R) grading on the tumor biopsy is considered to high:

• N0, Her2neu negative, <35 years, ≤1cm (T1a/b) with B&R grade 1 or 2 on biopsy.
• N0 Her2neu negative, ER/PR negative (triple negative), 35-70yr, 1.1-2cm (T1c) with B&R grade 1 or 2 on biopsy.
• N0, Her2neu negative, ER/PR positive > 50%, ductal carcinoma, 60-70yr, 1.1-2cm (T1c), with B&R grade 3 on biopsy and if the MammaPrint is not reimbursed by health insurance also for grade 1 on biopsy.
• N0, Her2neu negative, ER/PR positive, ductal carcinoma, 35-60yr, 1.1-2cm (T1c) with B&R grade 1 on biopsy.
• N0, Her2neu negative, ER/PR positive, but ≤50%, ductal carcinoma, 60-70yr, 1.1-2cm (T1c) with B&R grade 1.

The following group of patients will be excluded based on the results of the MammaPrint:

• Only if the MammaPrint is reimbursed by health insurance: N0, Her2neu negative, ER/PR positive, > 50% ductal carcinoma, 60-70yr, 1.1-2cm (T1c), with B&R grade 1 and MammaPrint high risk.

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: MR-HIFU ablation; Ten patients undergo MR-HIFU ablation with the Sonalleve MR-HIFU Breast Tumor Therapy System (Profound Medical). According to a treat-and-resect protocol, these patients also undergo standard therapy consisting of breast cancer surgery 1 to 2 weeks after MR-HIFU treatment (+/- radiotherapy).	Device: Philips Sonalleve MR-HIFU Breast Tumor Therapy System; Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) is a completely non-invasive treatment technique. HIFU uses focused ultrasound to achieve temperature rise in the targeted tissue. Real time monitoring of the treatment with MR-thermometry is used to ensure optimal safety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of ablated tissue at histopathological examination	The amount of ablated tissue and residual viable tumor tissue will be assessed in all tumor slices.	2-3 weeks (after surgery is performed)
Presence of non-perfused volumes on DCE-MRI	Efficacy will be assessed by the presence of non-perfused volumes on DCE-MRI. A pre-treatment MRI is used as comparison.	1 week after MR-HIFU ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events	Adverse events will be documented. The (possible) relationship with MR-HIFU ablation will be asessed in all cases.	Approximately 2 to 3 weeks

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Manon NG Braat, MD, UMC Utrecht

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: March 30, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; ablation; MR-HIFU; non-invasive treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NL46863.041.14