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

Official Summary

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 Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 8 participants

Interventions

• 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

Primary Outcomes

• Adverse events (Throughout the study, approximately 10 months.)

Secondary Outcomes

• Feasibility of BBBD (Immediately after each BBBD procedure)

Eligibility Criteria

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

Trial Locations

• Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

More Breast Cancer Trials

View all Breast Cancer clinical trials