Clinical Trials /

Convection-Enhanced Delivery of 124I-Omburtamab for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

NCT01502917

Description:

The purpose of this study is to test the safety of a new method to treat Diffuse Intrinsic Pontine Glioma (DIPG). The researchers will use "convection-enhanced delivery" (CED) to deliver an agent called 124I-omburtamab. CED is performed during surgery. The study agent is infused through a small tube placed into the tumor in the brain. Many studies have shown this can safely be done in animals but this study is the first time 124I-omburtamab will be given by CED in humans. This will be one of the first times that CED has been performed in the brain stem. Omburtamab is something called an antibody. Antibodies are made by the body to fight infections and sometimes cancer. The antibody omburtamab is produced by mice and can attack many kinds of tumors. A radioactive substance, 124I-omburtamab, is attached to omburtamab. 124I-omburtamab sticks to parts of tumor cells and can cause the tumor cells to die from radiation. Studies have also been done on humans using 124I-omburtamab to treat other kinds of cancer. Our studies of some DPG and related tumors suggest that omburtamab will bind to the tumor, but the investigators don't know that for sure. In this study, the researchers want to find out how safe 124I-omburtamab given by CED is at different dose levels. They will look to see what effects (both good and bad) it has on the patient. The dose of 124I-omburtamab will increase for each new group of patients. The procedure has already been safely performed with lower doses and infusion volumes in a number of patients here at MSKCC. The amount they get will depend on when they enter the study. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some more patients may be treated with a lower dose to make sure that dose is safe.

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01502917

Trial Eligibility

Document

Title

  • Brief Title: Convection-Enhanced Delivery of 124I-Omburtamab for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy
  • Official Title: A Phase I Study of Convection-Enhanced Delivery of 124I-Omburtamab for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

Clinical Trial IDs

  • ORG STUDY ID: 11-011
  • NCT ID: NCT01502917

Conditions

  • Brain Cancer
  • Brain Stem Glioma

Interventions

DrugSynonymsArms
Radioactive iodine-labeled monoclonal antibody omburtamabRadioactive iodine-labeled monoclonal antibody omburtamab

Purpose

The purpose of this study is to test the safety of a new method to treat Diffuse Intrinsic Pontine Glioma (DIPG). The researchers will use "convection-enhanced delivery" (CED) to deliver an agent called 124I-omburtamab. CED is performed during surgery. The study agent is infused through a small tube placed into the tumor in the brain. Many studies have shown this can safely be done in animals but this study is the first time 124I-omburtamab will be given by CED in humans. This will be one of the first times that CED has been performed in the brain stem. Omburtamab is something called an antibody. Antibodies are made by the body to fight infections and sometimes cancer. The antibody omburtamab is produced by mice and can attack many kinds of tumors. A radioactive substance, 124I-omburtamab, is attached to omburtamab. 124I-omburtamab sticks to parts of tumor cells and can cause the tumor cells to die from radiation. Studies have also been done on humans using 124I-omburtamab to treat other kinds of cancer. Our studies of some DPG and related tumors suggest that omburtamab will bind to the tumor, but the investigators don't know that for sure. In this study, the researchers want to find out how safe 124I-omburtamab given by CED is at different dose levels. They will look to see what effects (both good and bad) it has on the patient. The dose of 124I-omburtamab will increase for each new group of patients. The procedure has already been safely performed with lower doses and infusion volumes in a number of patients here at MSKCC. The amount they get will depend on when they enter the study. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some more patients may be treated with a lower dose to make sure that dose is safe.

Trial Arms

NameTypeDescriptionInterventions
Radioactive iodine-labeled monoclonal antibody omburtamabExperimentalThis is a therapeutic Phase I study intended to assess the safety of convection-enhanced delivery (CED) of radioimmunotherapy in the treatment of children with diffuse pontine glioma.
  • Radioactive iodine-labeled monoclonal antibody omburtamab

Eligibility Criteria

        Inclusion Criteria:

          -  Consensus of diagnosis must be reached by a multidisciplinary pediatric neuro-oncology
             team by considering both clinical evidence and MRI presentation. Tissue diagnosis is
             not required.

          -  The patient must have undergone prior external beam radiotherapy to a dose of 54-60 Gy
             to the brain stem. At least 4 weeks but no more than 14 weeks must have elapsed from
             the completion of radiotherapy.

          -  The patient must be in adequate general condition for study, with Lansky or Karnofsky
             Performance Score of ≥ 50 at study entry .

        Lansky Performance scale will be used for patients ≤16 years of age.

          -  The patient must be ≥ 2 and ≤ 21 years old.

          -  Patient must weigh a minimum of 8 kg.

        Exclusion Criteria:

          -  Clinical and/or radiographic (MRI) progression of tumor following external beam
             radiation therapy.

          -  Metastatic disease.

          -  Untreated symptomatic hydrocephalus determined by treating physician.

          -  AST or ALT > 2x the upper limit of normal.

          -  Platelets < 100,000/mcL.

          -  ANC < 1000/mcL.

          -  Abnormal PT (Inr) >1.5 INR or PTT > 42 sec (may be corrected with FFP,
             cryoprecipitate, vitamin K, etc).

          -  Total bilirubin > 2.0 mg/dl.

          -  Serum creatinine > 1.5x the upper limit of normal for age, or calculated creatinine
             clearance or nuclear GFR < 70 ml/min/1.73 m2.
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximum tolerated dose
Time Frame:2 years
Safety Issue:
Description:Determination that a dose is safe will be made following the treatment of at least 3 but no more than 6 patients at a particular dose level. The dose levels are DL1 (0.25 mCi), DL2 (0.5 mCi), DL3 (0.75 mCi), DL4 (1.0 mCi) DL5 (2.5mCi), DL6 (3.25mCi), DL7 (4.0mCi), DL 7.1(4.0mCi), DL 7.2 (4.0mCi), DL 8 (6.0mCi), DL 9 (8.0mCi), DL 10 (10.0mCi), DL 11 (12.0mCi) ,fallback DL0 (0.125 mCi) FB1 (1.50mCi) and FB2 (2.0mCi). An incidence of dose-limiting toxicity (DLT) in the range of 25% is considered acceptable in this population. A maximum tolerated dose (MTD) will be defined as the dose level below that at which 2 DLTs have occurred.

Secondary Outcome Measures

Measure:overall survival
Time Frame:2 years
Safety Issue:
Description:Overall survival from the time of diagnosis will be recorded for every patient in this study. Overall survival will be estimated by Kaplan-Meier methodology.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Y-mAbs Therapeutics

Trial Keywords

  • Brain stem glioma
  • CNS
  • MAB 124I-omburtamab
  • infusion cannula
  • DIPG
  • Diffuse Intrinsic Pontine Glioma
  • 11-011

Last Updated

June 11, 2021