Clinical trial NCT01502917: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Cancer
Brain Stem Glioma
Keywords: Brain stem glioma
CNS
MAB 124I-omburtamab
infusion cannula
DIPG
Diffuse Intrinsic Pontine Glioma
11-011
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Memorial Sloan Kettering Cancer Center
First posted: 2012-01-02
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


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.

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 2 years
measure: assess the toxicity profile
timeFrame: 2 years
Secondary outcomes:
measure: overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Mark Souweidane, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.