We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04264143
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : March 10, 2022
Sponsor:
Collaborator:
Midatech Pharma US Inc.
Information provided by (Responsible Party):
Luca Szalontay, Columbia University

Tracking Information
First Submitted Date  ICMJE February 7, 2020
First Posted Date  ICMJE February 11, 2020
Last Update Posted Date March 10, 2022
Actual Study Start Date  ICMJE March 10, 2020
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Incidence of Adverse Events [ Time Frame: Up to six weeks after second infusion ]
    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.
  • Maximum Tolerated Dose (MTD) of MTX110 [ Time Frame: 14 days ]
    The MTD will be determined based on the number of dose limiting toxicities (DLT) observed in each of the titrated doses.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Steady state volume of drug distribution [ Time Frame: 14 days ]
    Measured by volumetric contrast enhancement intensity on MRI and magnetic resonance (MR) spectroscopy
  • Time to tumor progression/recurrence (PFS) [ Time Frame: 2 years ]
    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.
  • Overall survival (OS) or time to death [ Time Frame: 2 years ]
    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.
  • Score on PedsQL 4.0 Brain Tumor Module [ Time Frame: 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Intrinsic Pontine Glioma
  • Diffuse Pontine and Thalamic Gliomas
  • Diffuse Midline Glioma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: MTX110 and CED
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.
Interventions:
  • Drug: Infusate with MTX110 and gadolinium
  • Device: Convection-Enhanced Delivery (CED)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2020)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2024
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Luca Szalontay, MD (212) 305-9770 ls3399@cumc.columbia.edu
Contact: Jessica Morcone, RNP 212-305-9770 jm4393@cumc.columbia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04264143
Other Study ID Numbers  ICMJE AAAS2936
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Luca Szalontay, Columbia University
Original Responsible Party Stergios Zacharoulis, Columbia University, Herbert and Florence Irving Associate Professor of Pediatric Neuro-Oncology
Current Study Sponsor  ICMJE Luca Szalontay
Original Study Sponsor  ICMJE Stergios Zacharoulis
Collaborators  ICMJE Midatech Pharma US Inc.
Investigators  ICMJE
Principal Investigator: Luca Szalontay, MD Columbia University
PRS Account Columbia University
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP