CED of MTX110 Newly Diagnosed Diffuse Midline Gliomas
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|ClinicalTrials.gov Identifier: NCT04264143|
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : February 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Intrinsic Pontine Glioma Diffuse Pontine and Thalamic Gliomas Diffuse Midline Glioma||Drug: Infusate with MTX110 and gadolinium Device: Convection-Enhanced Delivery (CED)||Phase 1|
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 :||Interventional|
|Estimated Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||April 2020|
|Estimated Primary Completion Date :||February 2022|
|Estimated Study Completion Date :||February 2024|
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.
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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04264143
|Contact: Stergios Zacharoulis, MDfirstname.lastname@example.org|
|Contact: Chankrit Sethi, MPHemail@example.com|
|United States, New York|
|Columbia University Irving Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Stergios Zacharoulis, MD 212-305-9005 firstname.lastname@example.org|
|Contact: Chankrit Sethi, MPH 212-305-4030 email@example.com|
|Principal Investigator: Stergios Zacharoulis, MD|
|Principal Investigator:||Stergios Zacharoulis, MD||Columbia University|