Clinical Trials /

MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma

NCT03566199

Description:

This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
Recruiting Status:

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MTX110 by Convection-Enhanced Delivery in Treating Participants With Newly-Diagnosed Diffuse Intrinsic Pontine Glioma
  • Official Title: An Open Label Single Arm Phase I/II Study of MTX110 Delivered by Convection-enhanced Delivery (CED) in Patients With Diffuse Intrinsic Pontine Glioma (DIPG) Previously Treated With External Beam Radiation Therapy

Clinical Trial IDs

  • ORG STUDY ID: 170817
  • SECONDARY ID: NCI-2018-01085
  • SECONDARY ID: PNOC015
  • NCT ID: NCT03566199

Conditions

  • Diffuse Intrinsic Pontine Glioma

Interventions

DrugSynonymsArms
Panobinostat Nanoparticle Formulation MTX110MTX-110, MTX110 (CN)Treatment (MTX110)
Convection-Enhanced Delivery (CED)CEDTreatment (MTX110)

Purpose

This phase I/II trial studies the side effects of panobinostat nanoparticle formulation MTX110 (MTX110) in treating participants with newly-diagnosed diffuse intrinsic pontine glioma. Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of repeated administration of MTX110 co-infused
      with gadoteridol given by intratumoral convection enhanced delivery in children with newly
      diagnosed diffuse intrinsic pontine glioma (DIPG).

      SECONDARY OBJECTIVES:

      I. To determine the clinical efficacy of repeated administration of MTX110 given by
      intratumoral convection-enhanced delivery (CED) in children with newly diagnosed DIPG in the
      confines of a phase I and early efficacy study.

      OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

      Participants receive panobinostat nanoparticle formulation MTX110 intratumorally (IT) by CED
      infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks
      for up to 24 months in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment participants are followed up at 30 days and then every 2
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (MTX110)ExperimentalParticipants receive panobinostat nanoparticle formulation MTX110 IT by CED infusion on day 1 or days 1 and 2 as determined by dose level. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
  • Panobinostat Nanoparticle Formulation MTX110
  • Convection-Enhanced Delivery (CED)

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with newly diagnosed DIPG by magnetic resonance imaging (MRI); defined as
             patients with a pontine location and diffuse involvement of at least 2/3 of the pons
             are eligible without histologic diagnosis. For lesions with typical imaging features,
             biopsy is neither encouraged nor required for eligibility. Tumors that are biopsied
             will be eligible if proven to be supportive of the diagnosis of a DIPG. Consensus of
             diagnosis by the study team must be met.

          -  Patients who have completed focal radiotherapy within 14 weeks from time of enrollment
             are eligible.

          -  Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after,
             the date of completion of focal radiotherapy.

          -  Prior chemotherapy: Patients should be at least 30 days from last chemotherapy dose
             prior to start of CED infusion, with exception of antibody half-lives. For antibody
             therapies, at least 3 half-lives of the antibody after last dose of monoclonal
             antibody should have passed prior to CED infusion. Patients less than 30 days from
             last chemotherapy dose should be discussed with the study chair(s).

          -  Prior radiation: Patients must have received prior treatment with focal radiotherapy
             as part of initial treatment for DIPG and had their last dose at least 4 weeks prior
             to and no later than 14 weeks from the first CED treatment. Standard focal radiation
             therapy will include 54 to 60 Gy by external beam radiotherapy to the brainstem.

          -  Age ≥ 2 years of age to 21 years. Patients younger than 3 years of age may be enrolled
             on study at the discretion of the Study Chair(s) if supporting evidence that brainstem
             lesion represents a brainstem glioma.

          -  Karnofsky Performance Score ≥ 50 for patients > 16 years of age and Lansky Performance
             Score ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of
             paralysis, but who are able to mobilize using a wheelchair, will be considered
             ambulatory for the purpose of assessing the performance score.

          -  Life expectancy of greater than 12 weeks measured from the date of completion of
             radiotherapy.

          -  Corticosteroids: Patients who are receiving dexamethasone must be on a stable or
             decreasing dose for at least 1 week prior to registration.

          -  Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3.

          -  Hemoglobin ≥ 8g/dl.

          -  Platelet count ≥ 100,000/mm^3 (transfusion independent, defined as not receiving
             platelet transfusions for at least 7 days prior to enrollment).

          -  Normal coagulation defined as normal International Normalized Ratio (INR) or per
             institutional guidelines.

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 milliliters
             (mL)/minute (min)/1.73 m^2.

          -  A serum creatinine (mg/dL) based on age/gender as follows:

               -  Age: 2 to < 6 years; Male: 0.8; Female: 0.8

               -  Age: 6 to < 10 years; Male: 1; Female: 1

               -  Age: 10 to < 13 years; Male: 1.2; Female: 1.2

               -  Age: 13 to < 16 years; Male:1.5; Female: 1.4

               -  Age ≥ 16 years; Male: 1.7; Female: 1.4

          -  Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for
             age.

          -  Serum glutamate pyruvate transaminase (SGPT) [alanine aminotransferase (ALT)] ≤ 110
             U/L.

          -  Serum albumin ≥ 2 g/dL.

          -  Patients with seizure disorder may be enrolled if on non-enzyme inducing
             anticonvulsants and well controlled.

          -  The effects of MTX110 on the developing human fetus are unknown. For this reason women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry, for the duration
             of study participation and 4 months after completion of MTX110 injection
             administration. Should a woman become pregnant or suspect she is pregnant while she or
             her partner is participating in this study, she should inform her treating physician
             immediately.

          -  Able to understand, and willing to sign, a written informed consent document.

          -  Patients who are unable to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy.

        Exclusion Criteria:

          -  Patients who had clinical and/or radiographic (MRI) progression of tumor following
             external beam radiation therapy.

          -  Patients with metastatic disease, including leptomeningeal or subarachnoid
             disseminated disease.

          -  Patients with tumor morphology that predicts poor coverage of the majority of the
             tumor including bilateral thalamic involvement, or cysts that represent > 50% of
             cross-sectional areas of the pons. These subjects should be discussed with the study
             chairs.

          -  Patients who are receiving any other investigational agents or other tumor-directed
             therapy.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MTX110 or gadolinium.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Female patients of childbearing potential must not be pregnant or breast-feeding.
             Female patients of childbearing potential must have a negative serum or urine
             pregnancy test within 14 days of registration.

          -  Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded;
             the assessment of mass effect should be made by the study chairs and study
             neurosurgeons prior to any planned CED treatment.

          -  Untreated symptomatic hydrocephalus determined by treating physician.

          -  Patients with evidence of intra-tumoral hemorrhage > 5 mm maximal diameter. These
             subjects should be discussed with the study chair.

          -  Subjects with prolonged corrected QT (QTc) (> 450 msec) will be excluded from the
             study.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of repeated convection-enhanced delivery (CED) of MTX110 following standard of care focal radiotherapy
Time Frame:up to 5 years
Safety Issue:
Description:Safety of repeated convection-enhanced delivery (CED) of MTX110 following standard of care focal radiotherapy will be reported by summarizing the incidence of adverse events by maximum intensity and relationship to study drug. Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcome Measures

Measure:Overall survival at 12 months
Time Frame:Up to 12 Months
Safety Issue:
Description:Analyses will be performed after all enrolled subjects have completed 12 months, or whenever the status of all subjects has been established, whichever comes first.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sabine Mueller, MD, PhD

Last Updated

October 11, 2019