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

Prior treatment

• Tumor not visible on any pre-therapy or post-radiation imaging
• Previous participation in other chemotherapy, molecularly targeted therapy, or immunotherapy treatment-related phase 1 or 2 trials
• Subject receiving bevacizumab (Avastin) therapy or increasing doses of steroids
• Anti-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 treatment
• Immunosuppression (corticosteroids to prevent/treat brain edema are permitted).
• Active seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by history
• Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
• Patients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study

Other illness

• Subject with metastatic disease
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
• Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
• Patients with positive HIV status
• Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol

Age

• Hypertension per age
• Severely impaired renal function with estimated glomerular filtration rate \<2 standard deviations for age

Other

• Symptoms and signs of increased intracranial pressure
• Subject with ventricular peritoneal shunt
• Known sensitivity to gadolinium-based contrast agents
• Contraindication to Doxorubicin
• Patients that may require trastuzumab during the study

• Age between 5 and 21 years, inclusive. Subjects younger than 5 years old may be eligible after discussion with the Sponsor Medical Monitor/designee (i.e. DSMB).
• Patient diagnosed with DIPG
• At least 4-week and not greater than 12 weeks from completion of radiation therapy
• Post-radiation imaging does not show evidence of necrosis/ hemorrhage or other features that contraindicate MRgFUS
• If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable
• If on steroids, stable or decreasing dose for at least 7 days prior to study entry
• Stable or improving neurologic status for 7 days prior to study entry
• Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
• Able to attend all study visits and with life expectancy of at least 6 months