Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound

InSightec

Status

Active, not recruiting

Conditions

Brain Tumor

Treatments

Device: Transcranial ExABlate

Study type

Interventional

Funder types

Industry

Identifiers

NCT02343991

BBB001

215600 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety of BBB disruption using transcranial MRI-guided focused ultrasound in conjunction with an intravenous ultrasound contrast agent to increase the accumulation of doxorubicin in brain tumours and the adjacent brain using the ExAblate Transcranial system (220 kHz). Data will be collected to establish the basic safety of this type of treatment as the basis for later studies to evaluate its clinical efficacy.

Enrollment

10 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men or women.
Age between 18 and 70 years, inclusive.
Able and willing to give informed consent.
Size of the targeted portion of the tumour (i.e. prescribed ROT) is less than 2.5 cm in diameter (16 cm3). The non-targeted tumour tissue may exceed the targeted volume.
Karnofsky rating 70-100
ASA score 1-3.
Able to communicate sensations during the ExAblate MRgFUS 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.

Exclusion criteria

The sonication pathway to the tumour involves:

i. More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp 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 below the lower limit of normal v. History of a hemodynamically unstable cardiac arrythmia vi. Cardiac pacemaker
Severe hypertension (diastolic BP > 100 on medication)
Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g.:ASA, non-steroidal anti-inflammatory drugs (NSAIDs), statins)
History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
Abnormal level of platelets (< 100000), PT (>14) or PTT (>36), and INR > 1.3
Documented cerebral infarction within the past 12 months
TIA in the last 1 month
Cerebral or systemic vasculopathy
Insulin-dependent diabetes mellitus
Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)
Known sensitivity to gadolinium-DTPA
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 with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis
Right to left or bi-directional cardiac shunt
Previous full course of doxorubicin chemotherapy
Allergy to eggs or egg products