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 Type2.0/2.1 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

Inclusion Criteria:Age between 5 and 21 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 MRgFUSIf brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stableIf on steroids, stable or decreasing dose for at least 7 days prior to study entryStable or improving neurologic status for 7 days prior to study entryAble and willing to give consent and/or assent or have a legal guardian who is able and willing to do soAble to attend all study visits and with life expectancy of at least 6 monthsExclusion Criteria:Tumor not visible on any pre-therapy or post-radiation imagingPrevious participation in other chemotherapy, molecularly targeted therapy, or immunotherapy treatment-related phase 1 or 2 trialsSymptoms and signs of increased intracranial pressureSubject with metastatic diseaseSubject with ventricular peritoneal shuntSubject receiving bevacizumab (Avastin) therapy or increasing doses of steroidsAnti-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 treatmentHistory of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.Hypertension per ageCerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitisImmunosuppression (corticosteroids to prevent/treat brain edema are permitted).Patients with positive HIV statusActive seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by historyKnown sensitivity to gadolinium-based contrast agentsKnown sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycolContraindication to DoxorubicinPrevious treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenedionesSeverely impaired renal function with estimated glomerular filtration rate <2 standard deviations for agePatients that may require trastuzumab during the studyPatients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study