CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas
Condition: Diffuse Intrinsic Pontine Glioma; Diffuse Pontine and Thalamic Gliomas; Diffuse Midline Glioma
MeSH terms: Glioma; Diffuse Intrinsic Pontine Glioma
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Infusate with MTX110 and gadolinium; Convection-Enhanced Delivery (CED)
Intervention type(s): Drug; Device
Intervention description(s): 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.; CED is the method by which the drug are delivered to the brain under controlled pressure to the brain by targeted micro-catheters.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Blood brain barrier; Diffuse Midline Gliomas; Convection-Enhanced Delivery (CED); Diffuse Intrinsic Pontine Glioma; Thalamic Gliomas