Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases (BBBD)

A Study to Evaluate the Safety and Feasibility of Blood-Brain Barrier Disruption Using MRI-Guided Focused Ultrasound in the Treatment of Her2-positive Breast Cancer Brain Metastases

The purpose of this study is to evaluate the safety of BBB disruption using the ExAblate 4000-system Type 2 in patients with Her-2 positive breast cancer metastases in the brain.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Brain Metastases
• Intervention / Treatment: Device: ExAblate BBBD

Detailed Description

The goal of this prospective, single arm, non-randomized study is to evaluate the safety and feasibility of using the Exablate Model 4000 Type 2 "Neuro-System" as a tool to serially disrupt the blood brain barrier in a temporary and localized fashion in patients with breast cancer and brain metastases. Up to 10 patients will be recruited at Sunnybrook. Patients will be consented, screened, undergo up to 6 study Exablate BBBD treatment cycles, every 2-3 weeks based on their trastuzumab regimen. Follow-up will continue through 12 weeks following the last BBBD post-treatment and the subject's participation in the study will be complete.

Data will be collected to establish the basic safety of this type of treatment as the basis for later studies to evaluate clinical efficacy.

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

Contacts and Locations

• Study Contact: Name: Lisa Dye; Phone Number: 7742666280; Email: lisad@insightec.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Principal Investigator: Nir Lipsman, MD
      • Contact: Maheleth Llinus; Phone Number: 2476 416-480-6100; Email: maheleth.llinas@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women between 18 and 80 years of age
• Able and willing to give informed consent
• Metastatic Her2-positive breast cancer with brain metastases
• Karnofsky performance score 70-100
• ASA score 1-3
• Able to communicate sensations during the ExAblate BBBD procedure
• Able to attend all study visits (i.e., life expectancy of at least 3 months)
• At least 14 days passed since last brain surgery
• At least 6 weeks passed since last radiation treatment

Exclusion Criteria:

• Brain metastases not visible on the pre-therapy imaging

• The sonication pathway to the tumour involves:

  i. Extensive scalp scars ii. Clips or other metallic implanted objects in the skull or the brain, except shunts

• The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema)

• Cardiac disease or unstable hemodynamics including:

  i. Documented myocardial infarction within six months of enrolment ii. Unstable angina on medication iii. Congestive heart failure iv. Left ventricular ejection fraction < 50% v. Right-to-left, bidirectional, or transient right-to-left cardiac shunts vi. History of a hemodynamically unstable cardiac arrythmia vii. Cardiac pacemaker viii. Contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation

• Severe hypertension (diastolic BP > 100 on medication)
• Anti-coagulant therapy or medications known to increase risk of hemorrhage within washout period prior to treatment (i.e. antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment)
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
• Abnormal level of platelets (< 100000) or INR > 1.3
• Documented cerebral infarction within the past 12 months
• Transient Ischemic Attack (TIA) in the last 1 month
• Known allergy sensitivity or contraindications to gadolinium-diethylenetriamine penta-acetic acid (DTPA), CT contrast, or perflutren or trastuzumab
• Allergy to eggs or egg products
• Contraindications to MRI such as non-MRI-compatible implanted devices
• Large subjects not fitting comfortably into the MRI scanner (generally >250 lbs)
• Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia
• Untreated, uncontrolled sleep apnea
• Positive pregnancy test (for pre-menopausal women)
• Known life-threatening systemic disease
• Severely impaired renal function
• Respiratory: chronic pulmonary disorders, e.g. severe emphysema, chronic obstructive pulmonary disease (COPD), pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, subjects with a history of drug allergies
• Any illness or medical condition that in the investigator's opinion precludes participation in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• 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 BBBD; Using ExAblate Model 4000 Type-2 to temporarily disrupt the blood brain barrier in patients with Her-2 positive breast cancer and brain metastases	Device: ExAblate BBBD; Using ExAblate Model 4000 Type-2 to temporarily disrupt the blood brain barrier in patients with Her-2 positive breast cancer and brain metastases; Other Names: Exablate Neuro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Rate of adverse events following each treatment through end of study	Throughout the study, approximately 10 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of BBBD	The extent of BBB opening will be determined by the degree of contrast enhancement seen on post-procedure MRI with contrast agent	Immediately after each BBBD procedure

Collaborators and Investigators

• Sponsor: InSightec
• Investigators: Principal Investigator: Nir Lipsman, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: BT006; 277990 (Other Identifier: Health Canada)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No