NCT05762419

FUS Etoposide for DMG

A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 4 Years – 21 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 blood brain barrier, limiting their access from the systemic circulation into the brain. Systemic administration of high doses may increase delivery to the brain, but this approach risks significant side effects and systemic toxicities. Direct delivery of the drugs to the brain by injection into the parenchyma bypasses the blood brain barrier; however, drug distribution from the site of injection tends to be limited. The technique of using focused ultrasound with microbubbles and neuro-navigator-controlled sonication can temporarily open up the blood brain barrier and allow for a greater concentration of drug to reach the tumor, thus potentially improving response in patients. With the current study, the investigators are planning to evaluate the safety and feasibility of using focused ultrasound and open-space neuronavigator-controlled sonication to open one to two tumor sites. For the purpose of the study, investigators will be administrating oral etoposide in children with progressive diffuse midline glioma. This drug has a known toxicity profile, dose, and well-documented efficacy against many metastatic cancers. Successful opening and closing of the blood brain barrier will be confirmed with periodic magnetic resonance imaging (MRI).

Conditions

• Diffuse Intrinsic Pontine Glioma
• Diffuse Midline Glioma, H3 K27M-Mutant

Interventions

Type	Name	Description
DRUG	Etoposide; 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.
DEVICE	Focused 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.

Timeline

• Start date: 2023-06-05
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2023-03-09
• Last updated: 2026-01-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study