Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG

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 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

Inclusion Criteria:Age between 5 and 18 years, inclusivePatient diagnosed with DIPGAt least 4-week and not greater than 12 weeks from completion of radiation therapyPost-radiation imaging does not show evidence of necrosis/ hemorrhage or other features that contraindicate MRgFUSAble to attend all study visits and with life expectancy of at least 6 monthsAble and willing to give consent and/or assent or have a legal guardian who is able and willing to do soIf on steroids, stable or decreasing dose for at least 7 days prior to study entryIf brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stableExclusion Criteria:Evidence of cranial or systemic infectionKnown life-threatening systemic diseasePrevious treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenedionesContraindication to Doxorubicin. - Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol. - Known sensitivity to gadolinium-based contrast agentsActive seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by historyPatients with positive HIV status. - Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitisHypertension per ageHistory of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhageAnti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs [NSAIDs], statins) within washout period prior to treatmentPatient receiving bevacizumab (Avastin) therapy or increasing doses of steroidsSymptoms and signs of increased intracranial pressurePrevious participation in other chemotherapy, molecularly targeted therapy or immunotherapy treatment-related phase 1 or 2 trialsTumor not visible on any pre-therapy or post-radiation imaging