A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)
Columbia University
Summary
The blood brain barrier (BBB) prevents some drugs from successfully reaching the target tumor. Focused Ultrasound (FUS) using microbubbles and neuro-navigator controlled sonication is a non-invasive method of temporarily opening up the blood brain barrier to allow a greater concentration of the drug to reach into the brain tumor. This may improve response and may also reduce system side effects in the patient. The primary purpose of this study is to evaluate the feasibility of safely opening the blood brain barrier in children with progressive diffuse midline gliomas (DMG) treated with oral etoposide using focused ultrasound with microbubbles and neuro-navigator-controlled sonication. For the purpose of the study, the investigators will be opening up the blood brain barrier temporarily in one or two locations around the tumor using the non-invasive focused ultrasound technology, and administrating oral etoposide in children with progressive diffuse midline glioma.
Description
Diffuse midline gliomas constitute 10% of all pediatric central nervous system (CNS) tumors. Subjects with Diffuse Intrinsic Pontine Gliomas (DIPG) have a poor prognosis with a median survival that is usually reported to be 9 months, and nearly 90% of children die within 18 months from diagnosis. The mainstay of treatment is radiation to the primary tumor site. Surgical resection does not influence the outcome and is often not feasible in this part of the central nervous system. Many promising drugs for central nervous system disorders have failed to attain clinical success due to an intact b…
Eligibility
- Age range
- 4–21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Ages 4 - 21 years * Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami, and/or histological confirmation of H3K27M mutation of pontine or thalamic glioma. Subjects must have evidence of clinical and/or radiographic progression of disease. * Lansky performance status score of at least 60 for subjects 16 years of age or younger. * Ka…
Interventions
- DrugEtoposide; Oral, 50 Mg
Subjects will receive focused ultrasound sonication followed by once daily oral etoposide (50mg/m\^2/dose). Oral etoposide will be taken every day for 21 days, followed by one week of rest. For the first cycle, etoposide will be administered immediately following confirming of the blood brain barrier opening through contrast magnetic resonance imaging (MRI) which will occur within 4 hours of the focused ultrasound procedure. For subsequent cycles, etoposide will be administered immediately following the focused ultrasound procedure. Subjects may continue for a maximum of 4 cycles.
- DeviceFocused ultrasound with neuro-navigator-controlled sonication
Focused ultrasound sonication will be performed a maximum of three times a week for two weeks with two weeks of rest.
Location
- Columbia University Irving Medical CenterNew York, New York