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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 80 Years
Gender	All

More Inclusion & Exclusion 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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03714243
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	InSightec
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Nir Lipsman, MD
Principal Investigator Affiliation	Sunnybrook Health Sciences Centre
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Breast Cancer, Brain Metastases

Additional Details

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.

Arms & Interventions

Arms

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

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

Contact a Trial Team

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