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Diffuse Intrinsic Pontine GliomaPhase 1NCT04264143

CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas

A Phase 1 study testing Infusate with MTX110 and gadolinium and Convection-Enhanced Delivery (CED) in people with Diffuse Intrinsic Pontine Glioma and Diffuse Pontine and Thalamic Gliomas, run by Luca Szalontay at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 18 years
What is being tested?
Infusate with MTX110 and gadolinium and Convection-Enhanced Delivery (CED)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
10 Mar 2020to 22 Nov 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Irving Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
Infusate with MTX110 and gadolinium, Convection-Enhanced Delivery (CED)
Keywords
Blood brain barrier, Diffuse Midline Gliomas, Convection-Enhanced Delivery (CED), Diffuse Intrinsic Pontine Glioma, Thalamic Gliomas
Medical subject headings
Diffuse Intrinsic Pontine Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Infusate with MTX110 and gadoliniumDrug

    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.

  • 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.

Study groups in NCT04264143
Study groupRoleWhat they receive
MTX110 and CEDExperimentalAll 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.
Receives: Drug: Infusate with MTX110 and gadolinium; Device: Convection-Enhanced Delivery (CED)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to six weeks after second infusion

  2. 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.

    Measured: 14 days

Secondary outcomes (4)

  1. Steady state volume of drug distribution

    Measured by volumetric contrast enhancement intensity on MRI and magnetic resonance (MR) spectroscopy

    Measured: 14 days

  2. Time to tumor progression/recurrence (PFS)

    PFS is defined as the duration of time from start of MTX110 treatment to time of progression or death from any cause, whichever occurs first.

    Measured: 2 years

  3. Overall survival (OS) or time to death

    Overall survival is defined as the duration of time from the start of MTX110 treatment to death from any cause. OS will be measured by follow-up with a study participant every 3-6 months until death for any reason.

    Measured: 2 years

  4. Score on PedsQL 4.0 Brain Tumor Module

    The 24-item PedsQL 4.0 Brain Tumor Module encompasses six scales: (1) cognitive problems (seven items), (2) pain and hurt (three items), (3) movement and balance (three items), (4) procedural anxiety (three items), (5) nausea (five items), and (6) worry (three items). Each item is measured with a 5-point Likert scale from 0 (never a problem) to 4 (almost always a problem), which is then transformed on a scale from 0-100. Higher scores indicate lower problems and therefore a better outcome.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2020
  2. Study start10 Mar 2020
  3. Primary completion25 Apr 2022
  4. Study completion22 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04264143
Sponsor's protocol ID
AAAS2936
Status last verified
Dec 2023
First submitted
7 Feb 2020
Last updated
18 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Infusate with MTX110 and gadolinium and Convection-Enhanced Delivery (CED) in people with Diffuse Intrinsic Pontine Glioma and Diffuse Pontine and Thalamic Gliomas, run by Luca Szalontay at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (time frame: Up to six weeks after second infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04264143.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.

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