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| Name | Class |
|---|---|
| Memorial Sloan Kettering Cancer Center | OTHER |
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radioactive iodine-labeled monoclonal antibody omburtamab | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radioactive iodine-labeled monoclonal antibody omburtamab | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| maximum tolerated dose | 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. | 2 years |
| assess the toxicity profile | Adverse events (toxicity) will be assessed and classified according to the Clinical Terminology Criteria for Adverse Events version 4.0 (CTCAE). Generally, grade 3 toxicities interfere with activities of daily living (ADLs) and grade 4 toxicities are life-threatening. Grade 5 toxicities cause death. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| overall survival | 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. | 2 years |
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Inclusion Criteria:
Lansky Performance scale will be used for patients ≤16 years of age.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Souweidane, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Medical College of Cornell University | New York | New York | 10021 | United States | ||
| Memorial Sloan Kettering Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40306974 | Derived | Franca Velo A, Giantini Larsen A, Humm JL, Zanzonico P, Haque S, Souweidane M, Pandit-Taskar N. Determination of the Intralesional Distribution of Theranostic 124I-Omburtamab Convection-Enhanced Delivery in Treatment of Diffuse Intrinsic Pontine Glioma. J Nucl Med. 2025 Jun 2;66(6):886-891. doi: 10.2967/jnumed.124.267995. | |
| 39969230 |
| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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|
| External Beam Radiotherapy | Radiation | Standard radiation therapy is given 4-6 weeks prior to study entry. |
|
| New York |
| New York |
| 10065 |
| United States |
| 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. |
| 39142829 | Derived | Pandit-Taskar N, Zanzonico PB, Grkovski M, Donzelli M, Vietri SM, Horan C, Serencsits B, Prasad K, Lyashchenko S, Kramer K, Dunkel IJ, Souweidane MM. Theranostic Intratumoral Convection-Enhanced Delivery of 124I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry. J Nucl Med. 2024 Sep 3;65(9):1364-1370. doi: 10.2967/jnumed.123.266365. |
| 32977309 | Derived | 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. |
| 30579270 | Derived | 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. |
| 29914796 | Derived | 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. |
| 28686124 | Derived | 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. |
| 26939629 | Derived | 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. |
| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| D000080443 | Diffuse Intrinsic Pontine Glioma |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D020295 | Brain Stem Neoplasms |
| D015192 | Infratentorial Neoplasms |
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