131I-omburtamab Delivered by Convection-Enhanced Delivery in Patients With Diffuse Intrinsic Pontine Glioma

NCT05063357 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 102
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Omburtamab is a murine IgG1 monoclonal antibody, recognizing CD276 (also known as B7- H3). Omburtamab is 131I-labeled at designated radio pharmacies and will be provided as a final radiolabeled product to treatment site. The proposed intervention includes surgical placement using standard stereotactic techniques of a small caliber cannula into the tumor in the pons followed by positive pressure infusion (i.e. CED) of 131I-omburtamab. Iodine-131 conjugated omburtamab (131I-omburtamab) administered via the intracerebroventricular route for the treatment of metastatic CNS neuroblastoma was shown to be tolerable and improve survival. Furthermore, 124I-omburtamab administered by convection enhanced delivery (CED) was shown to have a tolerable safety profile in an ongoing dose escalation trial (in doses up to 4mCi) in patients with diffuse pontine gliomas that have not progressed following external beam radiation therapy. The aim of this trial is to determine the efficacy and safety of 131I-omburtamab in patients with DIPG that have not progressed following external beam radiation therapy.

Conditions

DIPG

Outcome Measures

Primary Outcomes (1)

• Determining the safety of up to 36 participants with 131I-omburtamab administered directly into the tumor by CED in patients with DIPG assessed by CTCAE v.5.0

  Up to 36 patients may be enrolled in the dose escalation phase in planned cohorts of 3 patients with a maximum of 3 cohorts at a dose level.All patients may receive up to three cycles of 131I-omburtamab. Patients will be followed until the last patient has had the last follow-up visit at 2 years after the 131I-omburtamab administration. End of trial is defined as last patient's last visit in the two-year follow-up period, or death whichever comes first. All Non-serious AEs should be reported from the time of CED placement surgery administration until 30 days after the IMP administration. All SAEs should be captured from signing the ICF until 30 days after IMP administration. Starting at day 31 after dosing of 131I-omburtamab only SAE's or ≥ grade 3 non-serious AEs considered at least possibly related to 131I-omburtamab or new onset of cancers regardless of causality should be reported.

  2 years after last patient has received final dose of 131I-omburtamab administration

Secondary Outcomes (11)

• Progression of tumor using Magnetic Resonance Imaging (MRI) of the brain in accordance with recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group for Diffuse Intrinsic Pontine Glioma (DIPG)

  60 months

• Progression of tumor using Magnetic Resonance Imaging (MRI) of the spine in accordance with recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group for Diffuse Intrinsic Pontine Glioma (DIPG)

  60 months

• Gross neurological investigation including the cranial nerves by physical examination and the Neurologic Assessment in Neuro-Oncology (NANO) scale.

  60 months

• SPECT/CT scans and blood sampling for dosimetry

  7 days

• Blood sampling for dosimetry

  7 days

Study Arms (1)

Radioactive iodine-labeled monoclonal antibody omburtamab

OTHER

Single arm

Drug: 131I-Omburtamab; Device: Convention Enhanced Delivery

Interventions

131I-Omburtamab DRUG

Omburtamab is a murine IgG1 monoclonal antibody, recognizing CD276 (also known as B7-H3).

Radioactive iodine-labeled monoclonal antibody omburtamab

Convention Enhanced Delivery DEVICE

The planned intervention includes surgical placement of a small caliber cannula into the tumor located in the pons using standard stereotactic techniques followed by CED of 131Iomburtamb.

Radioactive iodine-labeled monoclonal antibody omburtamab

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of diffuse intrinsic pontine glioma based on clinical evidence and radiographic (MRI) imaging.
• The patient must have undergone prior external beam radiotherapy using standard conformal fractionated or hypo-fractionated techniques to a planned maximal total dose of 54-60 Gy to the brain stem of which the patient must have received ≥ 90% of the planned dose, at least 4 weeks but no more than 14 weeks prior signing of ICF.
• Lansky or Karnofsky Performance Score of ≥ 70 at study entry. Lansky Performance scale to be used for patients ≤16 years of age.
• Age ≥ 3 years old and less than 21 years old.
• Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations.

You may not qualify if:

• Clinical and/or radiographic (MRI) progression of tumor in the period between external beam radiation therapy and signing of ICF. If pseudoprogression is suspected rescreening is allowed
• Metastatic or disseminated disease.
• Tumor size larger than 20cm3.
• Untreated symptomatic hydrocephalus as determined by the investigator
• Increasing dose of steroids for 1 week prior to first IMP treatment
• AST or ALT \> 3x the upper limit of normal.
• Total bilirubin \> 3x the upper limit of normal. In case either AST or ALT ≥3 x ULN, bilirubin must be ≤ 2 x the upper limit of normal.
• Hemoglobin less than 8 g/dL.
• White blood cell (WBC) count less than 1000/μL.
• ANC count less than 500/μL.
• Platelet count less than 100,000/μL.
• INR (international normalized ratio) higher than 1.5 (calculated from the prothrombin time).
• Glomerular filtration rate (eGFR) of ≤ 60 ml/min/1.73m2 calculated by 2009 revised Bedside Schwartz Equation.
• Weight less than 8kg.
• Life expectancy less than six weeks as judged by the investigator.

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead
• Labcorp Corporation of America Holdings, Inc: collaborator
• Invicro: collaborator

MeSH Terms

Interventions

omburtamab I-131

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, multi-center clinical trial

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 1, 2021
• Study Start: March 1, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 26, 2023

Record last verified: 2023-06