CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas

NCT04264143 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: AAAS2936
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Blood brain barrier; Diffuse Midline Gliomas; Convection-Enhanced Delivery (CED); Diffuse Intrinsic Pontine Glioma; Thalamic Gliomas

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  Safety of repeated convection-enhanced delivery (CED) of MTX110 will be reported by summarizing the incidence rate of adverse events observed or reported. Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to six weeks after second infusion

• Maximum Tolerated Dose (MTD) of MTX110

  The MTD will be determined based on the number of dose limiting toxicities (DLT) observed in each of the titrated doses.

  14 days

Secondary Outcomes (4)

• Steady state volume of drug distribution

  14 days

• Time to tumor progression/recurrence (PFS)

  2 years

• Overall survival (OS) or time to death

  2 years

• Score on PedsQL 4.0 Brain Tumor Module

  2 years

Study Arms (1)

MTX110 and CED

EXPERIMENTAL

All patients enrolled in the study will receive infusion of MTX110 and Gadolinium delivered by the CED delivery system directly into the tumor over 9-11 days.

Drug: Infusate with MTX110 and gadolinium; Device: Convection-Enhanced Delivery (CED)

Interventions

Infusate with MTX110 and gadolinium DRUG

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.

MTX110 and CED

Convection-Enhanced Delivery (CED) DEVICE

CED is the method by which the drug are delivered to the brain under controlled pressure to the brain by targeted micro-catheters.

MTX110 and CED

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Luca Szalontay: lead
• Midatech Pharma US Inc.: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Gadolinium

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Metals

Study Officials

• Luca Szalontay, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Herbert and Florence Irving Associate Professor of Pediatric Neuro-Oncology

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: March 10, 2020
• Primary Completion: April 25, 2022
• Study Completion: November 22, 2023
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)