The main objective of this study is to demonstrate treatment efficacy of MR-HIFU ablation of breast cancer. Effective treatment is defined as 100% necrosis of the targeted primary breast tumor. The secondary objective is safety of the MR-HIFU…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
- Breast disorders
- Breast therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is the efficacy of MR-HIFU for ablation of
breast tumors assessed by the amount of necrotic tumor tissue, which will be
determined by MRI and by histopathologic examination after resection.
Secondary outcome
The secondary endpoint is safety, assessed by reporting adverse events and by
NRS (numeric rating scale) after the MR-HIFU procedure.
Background summary
Breast-conserving therapy is standard of care for patients with localized
breast cancer. Nowadays there is growing interest to treat breast cancer
patients in a less invasive way, e.g. by radiofrequency, laser, microwave and
high intensity focused ultrasound (HIFU) ablation. Magnetic Resonance-guided
High-Intensity Focused Ultrasound (MR-HIFU) is a completely non-invasive
treatment technique. HIFU uses focused ultrasound waves for tumor ablation by
heating the cancerous tissue. Real time monitoring of the treatment with
Magnetic Resonance Imaging (MRI) is used to ensure optimal safety. Previous
MR-HIFU studies have shown low complication rates and quick recovery. Philips
Healthcare developed a dedicated MR-HIFU breast system for ablation of tumors
in the breast, the Philips Sonalleve MR-HIFU Breast Tumor Therapy System. In
2017 Profound Medical acquired Philips* MR-HIFU business and Profound Medical
has since then taken over responsibility as manufacturer of the MR-HIFU breast
system. A feasibility study in 10 patients assessing the treatment accuracy of
MR-HIFU ablation of malignant breast tumors has been performed at the UMC
Utrecht (METC no. 12-082). The results show that MR-HIFU ablation is a safe and
accurate treatment for malignant breast tumors. The next step is to prove the
efficacy of MR-HIFU ablation with the dedicated breast system, which must be
equal to conventional surgery to enable clinical implementation of this
treatment.
Study objective
The main objective of this study is to demonstrate treatment efficacy of
MR-HIFU ablation of breast cancer. Effective treatment is defined as 100%
necrosis of the targeted primary breast tumor. The secondary objective is
safety of the MR-HIFU treatment.
Study design
Single-center, single arm, non-randomized, intervention study.
Intervention
This study will be performed according to a treat-and-resect protocol. The
entire breast tumor including a 5 mm safety margin will be ablated with the
dedicated breast system. After 1-3 weeks, patients will undergo
(breast-conserving) surgery as standard clinical practice to ensure total
removal of cancerous tissue and to determine the efficacy of MR-HIFU ablation.
Patients are treated under procedural sedation analgesia (PSA) with Esketamine
and Propofol or Remifentanil and Propofol.
Study burden and risks
After signing informed consent, patients will undergo a conventional MRI scan
(1.5 or 3.0 Tesla) with a Gadolinium-Based Contrast Agent (GBCA) at the
outpatient clinic. This Dynamic Contrast-Enhanced MRI (DCE-MRI) scan is
required to determine whether a patient meets all additional HIFU treatment
inclusion criteria. Eligible patients will undergo HIFU treament. On the day of
treatment, patients will be admitted at the Radiology department. During
treatment, the patient lies in prone position on the table top of the dedicated
MR-HIFU breast system, integrated in an MRI bore. An intravenous catheter will
be used for the administration of sedatives and the Magnetic Resonance (MR)
contrast agent and an urinary catheter will be placed. After treatment patients
will be monitored in the hospital at the nursing unit of the Imaging division
for a few hours and discharged on the same day, or later if clinically
indicated. After one to two weeks after MR-HIFU treatment, a third DCE-MRI scan
will be performed to determine radiological response of the tumor. Digital
photographs of the breast will be made before and after the treatment to
evaluate cosmetic effects. Optionally, three blood samples will be obtained
once before and twice after the MR-HIFU procedure, if possible from an already
inserted intravenous catheter (otherwise via venipuncture). The samples will be
used for future research in the field of breast cancer and/or MR-HIFU
treatment, the tests are not all determined yet. Patients will undergo surgery
in one to three weeks after MR-HIFU treatment. They will receive additional
treatment with radiotherapy and/or chemotherapy and follow-up according to
standard clinical practice. The most important risks associated with
participation in this study include: thermal damage to the skin or pectoral
muscle, damage to lungs or heart and complications associated with PSA.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
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 of HIFU table
top., Additional HIFU treatment inclusion criteria based on MRI findings:
• The tumor is located within the reach of the HIFU beam.
• 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.
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 any contrast agent, renal failure (GFR <
30 ml/min/1,73m2).
• Contra-indications for procedural sedation analgesia with Propofol and
Eskatamine or Propofol and Remifentanil.
• Extensive intraductal components in the lesion determined by biopsy, defined
as a ratio of more than 0.5 when dividing the number of ducts or lobules
involved with carcinoma in situ by the number of tissue cores in the biopsy.
• Scar tissue or surgical clips in the HIFU beam path.
• Inability to lie in prone position.
• Pregnancy or lactation.
• Communication barrier with patient.
• 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., • 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02407613 |
| CCMO | NL46863.041.14 |