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

This is an interventional device feasibility trial for Breast Cancer Read More

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