Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of High Grade Glioma in Patients Undergoing Standard Chemotherapy

Protocol # :
Feasibility / Pilot
Disease Sites
Brain and Nervous System
Principal Investigator
Golby, Alexandra
Site Research Nurses
Anketell, Mary Beth
Chau, Johny, E.
Christie, Sarah
Cifrino, Meghan
Doherty, Lisa
Fontana, Brittney
Hogan, Sarah
Iuliano, Sherry
Lafrankie, Debra
Stefanik, Jennifer
Taubert, Christina, Elizabeth
Torres, Alexandra

Trial Description

The purpose of this study is to evaluate the safety of the ExAblate Model 4000 Type 2 used as
a tool to disrupt the BBB (blood brain barrier) in patients with high grade glioma undergoing
standard of care therapy.

Eligibility Requirements

Inclusion Criteria:

1. Patient is eligible for adjuvant temozolomide (TMZ) treatment based on the current
standard of care.

2. Men or women age between 18 and 80 years, inclusive.

3. Able and willing to give informed consent.

4. Grade IV glioma (GBM)

5. Combined radiation/TMZ treatment is completed based on the prescribed standard of care

6. Karnofsky rating 70-100.

7. Able to communicate during the ExAblate BBBD (Blood Brain Barrier Disruption)

8. Able to attend all study visits (i.e., life expectancy of at least 3 months).

Exclusion Criteria:

1. Patients presenting with the following imaging characteristics:

i. Evidence of acute intracranial hemorrhage.

2. The sonication pathway to the tumor involves:

i. Extensive scalp sores. ii. Clips or other metallic implanted objects in the skull
or the brain (brain implants)

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

4. Patients with cerebellar or brainstem tumors.

5. Patients with positive HIV status.

6. Significant depression not adequately controlled with medication and at potential risk
of suicide.

7. Patient receiving bevacizumab (Avastin) therapy.

8. Patients receiving treatment with corticosteroid doses greater than dexamethasone 24
mg daily (or equivalent).

9. Patients undergoing other concurrent therapies such as chemotherapy wafers,
immunotoxins delivered by convection-enhanced delivery, regionally administered gene
and viral therapies, immunotherapies, focal irradiation with brachytherapy,
stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment
fields therapy.

10. Cardiac disease or unstable hemodynamics including:

i. Documented myocardial infarction within six months of enrollment. ii. Unstable
angina on medication. iii. Congestive heart failure. iv. Left ventricular ejection
fraction <50%. v. History of a hemodynamically unstable cardiac arrhythmia. vi.
Cardiac pacemaker.

11. Severe hypertension (diastolic BP > 100 on medication).

12. Anti-coagulant therapy, or medications known to increase risk of hemorrhage within
washout period prior to treatment.

13. History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor

14. Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular
malformation, cerebral aneurysm or vasculitis.

15. History of drug or alcohol use disorder.

16. Active seizure disorder or epilepsy (seizures despite medical treatment).

17. Known sensitivity to gadolinium-based contrast agents.

18. Known sensitivity to DEFINITY® ultrasound contrast agent or perflutren.

19. Contraindications to MRI such as non-MRI-compatible implanted devices.

20. Large subjects not fitting comfortably into the MRI scanner.

21. Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.

22. Positive pregnancy test (women of childbearing potential).

23. Severely impaired renal function or on dialysis.

24. Cardiac shunt.

25. Subjects with evidence of cranial or systemic infection.

26. Subjects with significant liver dysfunction, e.g., history of cirrhosis or active