NCT04264143

CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas

A Phase I Study Examining the Feasibility of Intermittent Convection-Enhanced Delivery (CED) of MTX110 for the Treatment of Children With Newly Diagnosed Diffuse Midline Gliomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Luca Szalontay · Academic / Other
• Sex: All
• Age: 3 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

The blood brain barrier (BBB) prevents some drugs from successfully reaching the target source. Convection-Enhanced Delivery (CED) is a method of direct infusion of drugs under controlled pressure to the tumor that may reduce systemic side effects of drugs in the patient. The purpose of this Phase I study is to find the maximum tolerated dose of MTX110 (a water-soluble Panobinostat nanoparticle formulation) and Gadolinium that can be given safely in children with newly diagnosed diffuse midline gliomas. All patients enrolled in the study will receive infusion of MTX110 and Gadolinium delivered with a pump directly into the tumor over 9-11 days.

Detailed description

Diffuse midline gliomas (DMGs), 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 outcome and is often not feasible in this part of the central nervous system. Many promising drugs for central nervous system (CNS) disorders have failed to attain clinical success due to an intact blood brain barrier (BBB), limiting their access form 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 BBB, however, drug distribution form the site of injection tends to be limited. The convection-enhanced delivery (CED) of drugs describes the infusion of drugs under controlled pressure to the brain parenchyma via targeted microcatheter. This technique facilitates and deliver higher drug concentrations in brain tissue or tumor. The BBB can now operate to retain drug and to significantly reduce systemic side effects. In addition, the fact that panobinostat seems to be most efficacious clinically available drug against DIPG cells.

Conditions

• Diffuse Intrinsic Pontine Glioma
• Diffuse Pontine and Thalamic Gliomas
• Diffuse Midline Glioma

Interventions

Type	Name	Description
DRUG	Infusate with MTX110 and gadolinium	Pulses 1 and 2 will be prepared with 30, 60 or 90 uM concentration of MTX110. The infusate consists of gadolinium and MTX110 (30, 60, or 90 uM) at approximately 1:100 ratio.
DEVICE	Convection-Enhanced Delivery (CED)	CED is the method by which the drug are delivered to the brain under controlled pressure to the brain by targeted micro-catheters.

Timeline

• Start date: 2020-03-10
• Primary completion: 2022-04-25
• Completion: 2023-11-22
• First posted: 2020-02-11
• Last updated: 2023-12-18

Locations

1 site across 1 country: United States

Regulatory

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