Convection-Enhanced Delivery of 124I-Omburtamab for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01502917 |
|
Recruitment Status :
Completed
First Posted : January 2, 2012
Last Update Posted : May 27, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Brain Cancer Brain Stem Glioma | Drug: Radioactive iodine-labeled monoclonal antibody omburtamab Radiation: External Beam Radiotherapy | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 50 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Other |
| 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 |
| Actual Study Start Date : | December 2011 |
| Actual Primary Completion Date : | January 2022 |
| Actual Study Completion Date : | January 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 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.
|
Drug: 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. Radiation: External Beam Radiotherapy Standard radiation therapy is given 4-6 weeks prior to study entry. |
- maximum tolerated dose [ Time Frame: 2 years ]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.
- assess the toxicity profile [ Time Frame: 2 years ]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.
- overall survival [ Time Frame: 2 years ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 2 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01502917
| United States, New York | |
| Weill Medical College of Cornell University | |
| New York, New York, United States, 10021 | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Principal Investigator: | Mark Souweidane, MD | Memorial Sloan Kettering Cancer Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Y-mAbs Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01502917 |
| Other Study ID Numbers: |
11-011 |
| First Posted: | January 2, 2012 Key Record Dates |
| Last Update Posted: | May 27, 2022 |
| Last Verified: | May 2022 |
|
Brain stem glioma CNS MAB 124I-omburtamab infusion cannula |
DIPG Diffuse Intrinsic Pontine Glioma 11-011 |
|
Glioma Brain Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms |
Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Antibodies Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |