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

This is a prospective, single arm, non-randomized feasibility study to evaluate the safety, feasibility and preliminary efficacy of Blood Brain Barrier Disruption (BBBD) using the Exablate Type 2 system in pediatric patients with Diffuse Intrinsic Pontine Gliomas (DIPG) undergoing Doxorubicin chemotherapy. The study will be conducted at up to three sites in the United States. Patients will undergo 3 treatment cycles, approximately 4-6 weeks apart. The study aims to establish feasibility and safety of Exablate BBBD in conjunction with Doxorubicin in the treatment of pediatric DIPG and assess preliminary efficacy in this patient population.

Age

5–21

Sex

ALL

Healthy volunteers

Not accepted

You may be eligible if

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

You may not be if

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
Symptoms and signs of increased intracranial pressure
Subject with metastatic disease
Subject with ventricular peritoneal shunt
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
History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
Hypertension per age
Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
Immunosuppression (corticosteroids to prevent/treat brain edema are permitted).
Patients with positive HIV status
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
Known sensitivity to gadolinium-based contrast agents
Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol
Contraindication to Doxorubicin
Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
Severely impaired renal function with estimated glomerular filtration rate \<2 standard deviations for age
Patients that may require trastuzumab during the study
Patients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study

What this study is about