Clinical trial NCT05383872: Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects with GlioBlastoma Brain Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glioblastoma
Glioma
Liquid Biopsy
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2022-05-20
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: Through study completion, up to 1 year
measure: Correlation with Tumor Tissue
timeFrame: Up to 3 hours Post-BBBD
Secondary outcomes:
measure: Circulating Free DNA
timeFrame: Up to 3 hours Post-BBBD
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: University of Maryland, Baltimore & The University of Maryland Medical System
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Grossman School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas, Southwestern
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Rockefeller Neuroscience Center
state: West Virginia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
Study officials:
References: