Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With GlioBlastoma Brain Tumors

A Pivotal Study to Evaluate the Safety and Effectiveness of Exablate Model 4000 Using Microbubble Resonators to Temporarily Mediate Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With GlioBlastoma Brain Tumors

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type 2.0/2.1 for liquid biopsy in subjects with suspected Glioblastoma brain tumors

This is a prospective, multi-center, pivotal clinical trial to evaluate the safety and efficacy of targeted blood brain barrier disruption using Exablate Model 4000 Type 2 for liquid biopsy in subjects with suspected Glioblastoma brain tumors. The study will be conducted at up to 25 centers in the US.

Inclusion Criteria:

1. Male or Female subjects18-80 years of age who are able and willing to give informed consent, or whose legally authorized representative is willing to consent on their behalf
2. Subjects with stereotactically-targetable suspected new or recurrent glioblastoma tumor on pre-operative brain imaging scans
3. Subjects that are scheduled, or will be scheduled within 4 weeks, for surgical resection or biopsy per standard clinical tumor care
4. Karnofsky Performance Score >70
5. Able to communicate sensations during the Exablate BBBD procedure

Exclusion Criteria:

1. Subjects with inoperable tumors (e.g., tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem)

2. Multifocal tumors

3. Tumor morphology or other imaging findings that precludes the ability to sonicate the tumor volume (including significant tumor volume outside the treatment envelope or tumor volume that exceeds the maximum sonication volume allowed, i.e. currently 110 ccs at the treatment volume level). Concern for adequate tumor coverage by sonication based on tumor morphology should be discussed with the Sponsor.

4. MRI or clinical findings of:

   1. Active or chronic infection(s) or inflammatory processes
   2. Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages
   3. Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis

5. MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices

6. Significant cardiac disease or unstable hemodynamic status

   1. Documented myocardial infarction within six months of enrollment
   2. Unstable angina on medication
   3. Unstable or worsening congestive heart failure
   4. Documented left ventricular ejection fraction below the lower limit of normal
   5. History of a hemodynamically unstable cardiac arrhythmia
   6. Cardiac pacemaker

7. Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)

8. Undergoing anti-coagulant or anti-platelet therapy, or using 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).

9. History of bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding

10. Abnormal coagulation profile (Platelets < 80,000, PT >14, PTT >36, or INR > 1.3)

11. Known cerebral or systemic vasculopathy

12. Significant depression and at potential risk of suicide

13. Known sensitivity/allergy to gadolinium or DEFINITY/DEFINITY RT,

14. Active seizures despite medication treatment (defined as >1 seizure per week) which could be worsened by disruption of the blood brain barrier

15. Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning

16. Known positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis

17. Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess

18. Any contraindications to MRI scanning, including:

    1. Large subjects not fitting comfortably into the scanner
    2. Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia

19. Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2

20. Severe Respiratory Illness: chronic pulmonary disorders (e.g., severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area), subjects with a history of severe drug allergies, severe asthma or hay fever, or multiple allergies where the benefit/risk of administering DEFINITY/DEFINITY RT is considered unfavorable by the study physicians in relation to the product labeling for DEFINITY/DEFINITY RT

21. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device

22. Pregnancy or Lactation