CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas

• Status: Recruiting
• Trial end date: 2024-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stergios Zacharoulis
• Collaborator: Midatech Pharma US Inc.

Criteria

Inclusion Criteria:

• Aged more than 3 years up to the 18th birthday

• Radiological diagnosis of DIPG with tumor confined to the region of the pons or

• thalami without cystic changes or hematoma obstructing the planned catheter trajectories

• Radiological diagnosis of thalamic gliomas confined to bilateral thalami without cystic changes or hematoma obstructing the planned catheter trajectories

• Radiological features of DIPG: intrinsic, pontine based infiltrative lesion; hypointense in T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons

• No prior therapy is allowed other than involved field radiotherapy (54Gy) and cerebrospinal fluid (CSF) diversion for hydrocephalus, including endoscopic third ventriculostomy (ETV) or a ventriculo-peritoneal shunt. No concomitant medicine or therapies for treatment are permitted while the patient is enrolled in this study.

• Karnofsky performance status or Lansky play score of ≥70 assessed at diagnosis

• Total bilirubin: within normal institutional limits

• Aspartate Aminotransferase (AST)(SGOT)/Alanine Aminotransferase (ALT)(SGPT): ≤ 2.5 × institutional upper limit of normal (ULN)

• Creatinine: within normal institutional limits

• Creatinine clearance: ≥ 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal

• Absolute neutrophil count: ≥ 1,500/μL

• Platelet count: ≥ 100,000/μL - no transfusion within 7 days

• Hemoglobin level: ≥ 10g/dL - no transfusion within 7 days

• Partial Thromboplastin Time (PT) and activated partial thromboplastin time (APTT):

within normal institutional limits

• No documented current bleeding disorder

• No medical condition that would preclude general anesthesia

• No severe acute infection or unexplained febrile illness

• Not pregnant or nursing - negative serum pregnancy test if appropriate within 7 days of study entry (adequate contraceptive methods for females and males required)

• No documented allergy to compounds of similar chemical or biologic composition to MTX110 or gadolinium compounds

• Subjects with a history of seizures/epilepsy should be on anticonvulsant medication prior to the first operative procedure on study, with serum levels within a therapeutic range

• Subjects must be able to undergo MR-imaging with gadolinium-based contrast administration (e.g. no ferrous-containing implants, no pacemakers, etc.)

• All subjects or their legal guardians must sign a document of informed consent indicating their understanding of the investigational nature and the potential risks associated with this study. When appropriate, pediatric subjects will be included in all discussions in order to obtain verbal and written assent

Exclusion Criteria:

• Radiological evidence of distant disease outside the pons or thalami

• Radiological evidence of metastatic disease within the central nervous system (CNS) at diagnosis

• Subjects with an uncorrectable bleeding disorder

• Subjects with multifocal or leptomeningeal disease beyond the pons or the thalami

• Subjects with signs of impending herniation or an acute intratumoral hemorrhage

• Subjects that have received or are on concurrent chemotherapy or biologic therapy for the treatment of their tumor

• Subjects who are pregnant or breastfeeding

• Previous experimental or trial-based therapy

• Patients who are known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MTX110.

• Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk