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

NCT ID: NCT01502917

Last Updated: 2023-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2022-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Brain Cancer Brain Stem Glioma

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Radioactive iodine-labeled monoclonal antibody omburtamab

This 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.

Group Type EXPERIMENTAL

Radioactive iodine-labeled monoclonal antibody omburtamab

Intervention Type DRUG

Prior to treatment children will be pre-medicated with super-saturated potassium iodide \& liothyronine to prevent thyroid uptake of the therapeutic radioisotopes. The proposed intervention is a surgical procedure using interstitial infusion of the radiolabeled monoclonal antibody 124I-omburtamab into the brain stem tumor. This will be performed by stereotactic placement of a small caliber infusion cannula into the tumor followed by a slow infusion (CED) of 124I-omburtamab. Following treatment, these children will be monitored during inpatient hospitalization with clinical evaluations \& PET/CT or PET/MRI scans of the brain \& other organs. Clinical observations, intensive care unit monitoring, routine blood \& interval imaging studies (MRI \& PET/CT or PET/MRI scans) will be performed at predetermined time points. If the PET/CT scan happens to fall on a weekend or holiday, the scan may be done before or after at the discretion of the Study PI. This will not affect dosimetry interpretation.

External Beam Radiotherapy

Intervention Type RADIATION

Standard radiation therapy is given 4-6 weeks prior to study entry.

Interventions

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Radioactive iodine-labeled monoclonal antibody omburtamab

Prior to treatment children will be pre-medicated with super-saturated potassium iodide \& liothyronine to prevent thyroid uptake of the therapeutic radioisotopes. The proposed intervention is a surgical procedure using interstitial infusion of the radiolabeled monoclonal antibody 124I-omburtamab into the brain stem tumor. This will be performed by stereotactic placement of a small caliber infusion cannula into the tumor followed by a slow infusion (CED) of 124I-omburtamab. Following treatment, these children will be monitored during inpatient hospitalization with clinical evaluations \& PET/CT or PET/MRI scans of the brain \& other organs. Clinical observations, intensive care unit monitoring, routine blood \& interval imaging studies (MRI \& PET/CT or PET/MRI scans) will be performed at predetermined time points. If the PET/CT scan happens to fall on a weekend or holiday, the scan may be done before or after at the discretion of the Study PI. This will not affect dosimetry interpretation.

Intervention Type DRUG

External Beam Radiotherapy

Standard radiation therapy is given 4-6 weeks prior to study entry.

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role collaborator

Y-mAbs Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Souweidane, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Weill Medical College of Cornell University

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

References

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Souweidane MM, Bander ED, Zanzonico P, Reiner AS, Manino N, Haque S, Carrasquillo JA, Lyashchenko SK, Thakur SB, Lewis JS, Donzelli M, Cheung NV, Larson SM, Kramer K, Pandit-Taskar N, Dunkel IJ. Phase 1 dose-escalation trial using convection-enhanced delivery of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma. Neuro Oncol. 2025 Sep 17;27(8):2117-2126. doi: 10.1093/neuonc/noaf039.

Reference Type DERIVED
PMID: 39969230 (View on PubMed)

Bander ED, Ramos AD, Wembacher-Schroeder E, Ivasyk I, Thomson R, Morgenstern PF, Souweidane MM. Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma. J Neurosurg Pediatr. 2020 Sep 25;26(6):661-666. doi: 10.3171/2020.6.PEDS20280. Print 2020 Dec 1.

Reference Type DERIVED
PMID: 32977309 (View on PubMed)

Morgenstern PF, Zhou Z, Wembacher-Schroder E, Cina V, Tsiouris AJ, Souweidane MM. Clinical tolerance of corticospinal tracts in convection-enhanced delivery to the brainstem. J Neurosurg. 2018 Dec 21;131(6):1812-1818. doi: 10.3171/2018.6.JNS18854. Print 2019 Dec 1.

Reference Type DERIVED
PMID: 30579270 (View on PubMed)

Souweidane MM, Kramer K, Pandit-Taskar N, Zhou Z, Haque S, Zanzonico P, Carrasquillo JA, Lyashchenko SK, Thakur SB, Donzelli M, Turner RS, Lewis JS, Cheung NV, Larson SM, Dunkel IJ. Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol. 2018 Aug;19(8):1040-1050. doi: 10.1016/S1470-2045(18)30322-X. Epub 2018 Jun 18.

Reference Type DERIVED
PMID: 29914796 (View on PubMed)

Ivasyk I, Morgenstern PF, Wembacher-Schroeder E, Souweidane MM. Influence of an intratumoral cyst on drug distribution by convection-enhanced delivery: case report. J Neurosurg Pediatr. 2017 Sep;20(3):256-260. doi: 10.3171/2017.5.PEDS1774. Epub 2017 Jul 7.

Reference Type DERIVED
PMID: 28686124 (View on PubMed)

Guisado DI, Singh R, Minkowitz S, Zhou Z, Haque S, Peck KK, Young RJ, Tsiouris AJ, Souweidane MM, Thakur SB. A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas. AJNR Am J Neuroradiol. 2016 Jul;37(7):1367-73. doi: 10.3174/ajnr.A4713. Epub 2016 Mar 3.

Reference Type DERIVED
PMID: 26939629 (View on PubMed)

Related Links

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http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

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11-011

Identifier Type: -

Identifier Source: org_study_id