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This arm aims to estimate event-free survival (EFS) and overall survival (OS) following therapy with irinotecan, temozolomide, bevacizumab, and compartmental (intraOmmaya) radioimmunotherapy (cRIT) 131I-omburtamab in patients with recurrent medulloblastoma. Patients with recurrent medulloblastoma will undergo surgery if feasible prior to study entry, followed by Induction Chemotherapy with irinotecan, temozolomide, and bevacizumab on study as per the Children's Oncology Group (COG) trial ACNS0821. Following 2 or 4 courses of chemotherapy and if radiographic disease status is stable or improved, patients will receive 2 therapeutic doses of 50 mCi cRIT 131I-omburtamab during Radioimmunotherapy. Following Radioimmunotherapy, patients may resume to Maintenance Chemotherapy with irinotecan, temozolomide, and bevacizumab for up to 12 total courses of chemotherapy or until disease progression, whichever occurs sooner.

This is a feasibility cohort. The primary objective is to assess feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma and to assess dosimetry. Patients must have progressed after initial surgery, radiation therapy, or other therapies. Patients will undergo surgery (if feasible) prior to study entry with the goal of achieving stable or better disease. Tumor tissue (archived or new) will be tested for B7H3 prior to enrollment. If positive, patients will enroll on Stratum 2 and receive one dosimetry dose (2 mCi) of cRIT 131I-omburtamab with nuclear medicine scintigraphy using SPECT during the Dosimetry Course (14 days in length). Following the Dosimetry Course and within 2 weeks of the dosimetry dose, patients may continue to Radioimmunotherapy to receive 2 therapeutic doses (50 mCi) of cRIT 131I-omburtamab.

Irinotecan is a semisynthetic water-soluble analog of camptothecin (a plant alkaloid isolated from Camptotheca acuminata). Irinotecan is available in single-dose amber glass vials in 40 mg (2 mL) and 100 mg (5 mL), 300 mg (15 mL), and 500 mg (25 mL).

Patients on Stratum 1 will be given irinotecan at 50 mg/m2/day IV on Days 1 through 5 of each chemotherapy course.

An orally administered alkylating agent, a second generation imidazotetrazine. A prodrug of MTIC, temozolomide spontaneously decomposes to MTIC at physiologic pH. Exerts its effect by cross-linking DNA. Temozolomide capsules are available in six different strengths (5, 20, 100, 140, 180, 250 mg). The capsules vary in size, color, and imprint according to strength. In the US, capsules are packaged in 5-count and 14-count bottles.

Patients on Stratum 1 will be given temozolomide at 150 mg/m2/dose PO on Days 1-5 of each chemotherapy course.

Bevacizumab is a recombinant humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody. Bevacizumab is supplied as a clear to slightly opalescent, sterile liquid ready for parenteral administration. Each 400 mg (25 mg/mL, 16 mL fill) glass vial contains bevacizumab with phosphate, trehalose, polysorbate 20, and Sterile Water for Injection.

Patients on Stratum 1 will be given bevacizumab at 10 mg/kg/day IV on Days 1 and 15 of each chemotherapy course, with the exception of the last course of Induction Chemotherapy (i.e., Course 2 or 4) where it will be administered on Day 1 only.

Omburtamab is a murine IgG1 monoclonal antibody (mAb) against B7-H3 (CD276) manufactured by in vivo growth of the hybridoma cell line without the use of animal-derived components. Omburtamab will be radiolabeled with iodine-131 at a designated radiolabeling facility. 131I-omburtamab is supplied as a sterile, injectable, radioactive product in a vial. Each supplied vial will contain enough radioactivity to prepare 50 mCi of 131I-omburtamab, formulated in 3.5-4 mL of solution. 131I-omburtamab should be administered via an intraventricular access device (i.e., Ommaya catheter or programmable VP shunt). Radioimmunotherapy consists of 56 days.

Patients on Stratum 1 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 8 and 36 of Radioimmunotherapy.

Patients on Stratum 2 will receive a therapeutic dose of 50 mCi cRIT 131I-omburtamab on Days 1 and 29 of Radioimmunotherapy.

Omburtamab I-131

Liothyronine (or equivalent) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. Liothyronine (or equivalent) will be administered at 25 µg PO, NG, or G-tube (if weight \< 25 kg) or 50 µg PO, NG, or G-tube (if weight ≥ 25 kg) daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.

Liothyronine

SSKI (potassium iodide) will be given as premedication for 131I-omburtamab to prevent thyroid accumulation. SSKI (potassium iodide) will be administered as 7 drops (\~0.35 mL) PO, NG, or G-tube daily starting on Day 1 of Radioimmunotherapy (for Stratum 1 patients) or Day 1 of Dosimetry (for Stratum 2 patients), with a mandated minimum of 7 days before each 131I-omburtamab injection and 14 days after each 131I-omburtamab injection. On the day of the 131I-omburtamab injection, administer any time before the injection.

SSKI

Dexamethasone will be given as premedication for 131I-omburtamab to prevent possible meningeal inflammatory reaction. Starting within 24 hours prior to each 131I-omburtamab injection, dexamethasone will be administered orally at 0.5 mg (if weight \< 15 kg) or 1 mg (if weight ≥ 15 kg) twice-daily doses for a total of 6 doses to alleviate infusion-related AEs: Two doses starting 24 hours pre-131I-omburtamab injection, two doses on the day of the injection (can be given before or after), and two doses 24 hours post-131I-omburtamab injection.

An antipyretic (e.g., oral acetaminophen \[15 mg/kg, 650 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.

Antipyretic

An antihistamine (e.g., IV diphenhydramine \[1 mg/kg, 50 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.

Antihistamine

An anti-emetic (e.g., IV ondansetron \[0.25 mg/kg, 16 mg maximum\] or equivalent) will be given as premedication for 131I-omburtamab within 1 to 3 hours before each 131I-omburtamab injection.

anti-emetics

Matthias Karajannis, MD, MS

A Phase 2 study investigating the addition of cRIT 131I-omburtamab to irinotecan, temozolomide, and bevacizumab for patients with recurrent medulloblastoma. A feasibility cohort is included to assess the feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma.

Direct intraventricular delivery of radiolabeled tumor-specific antibodies may aid in both the detection and treatment of recurrent disease for these highly specific pediatric patients with recurrent tumors.

Stratum 1: This is a phase 2 single-arm open-label study that will define event-free survival (EFS) and overall survival (OS) following therapy with irinotecan, temozolomide, bevacizumab, and compartmental (intraOmmaya) radioimmunotherapy (cRIT) 131I-omburtamab in patients with recurrent medulloblastoma. Patients with recurrent medulloblastoma will undergo surgery if feasible prior to study entry, followed by Induction Chemotherapy with irinotecan, temozolomide, and bevacizumab on study as per the Children's Oncology Group (COG) trial ACNS0821. Following 2 or 4 courses of chemotherapy and if radiographic disease status is stable or improved, patients may continue to Radioimmunotherapy to receive 2 therapeutic doses (50 mCi each) of cRIT 131I-omburtamab. Following Radioimmunotherapy, patients may resume to Maintenance Chemotherapy with irinotecan, temozolomide, and bevacizumab for up to 12 total courses of chemotherapy or until disease progression, whichever occurs sooner. The primary comparison for this study will be the medulloblastoma cohort treated on ACNS0821 on the irinotecan + temozolomide + bevacizumab arm (N=52).

Stratum 2: This is a feasibility cohort. The primary objective is to assess feasibility of incorporating cRIT 131I-omburtamab for patients with recurrent ependymoma and to assess dosimetry. Patients must have progressed after initial surgery, radiation therapy, or other therapies. Patients will undergo surgery (if feasible) prior to study entry with the goal of achieving stable or better disease. Tumors (archived or new) will be tested for B7H3 prior to enrollment. If positive, patients will enroll on Stratum 2 and receive one dosimetry dose (2 mCi) of cRIT 131I-omburtamab with nuclear medicine scintigraphy (typically using 3 whole-body planar gamma camera imaging and at least 1 head SPECT scan or SPECT/CT) using SPECT during the Dosimetry Course (14 days in length). Following the Dosimetry Course and within 2 weeks of the dosimetry dose, patients may continue to Radioimmunotherapy to receive 2 therapeutic doses (50 mCi each) of cRIT 131I-omburtamab.

131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma

Phase 2 Study of Intraventricular Omburtamab-based Radioimmunotherapy for Pediatric Patients With Recurrent Medulloblastoma and Ependymoma

Using the Kaplan Meier method, estimate of event-free survival (EFS) of patients with relapsed medulloblastoma treated with the study regimen. EFS is defined as the interval of time between enrollment on the study and the minimum date of documentation of progressive disease, death due to any cause, subsequent malignancy or date of last follow-up.

Percentage of patients who met feasibility criteria of incorporating cRIT 131I-omburtamab treatment for patients with recurrent ependymoma. Patients who meet both of the following criteria will be counted as feasibility successes: 1) Administration of the first therapeutic dose of the antibody at the treating institution within 6 days of labeling. 2) Successful acquisition of all 3 SPECT scans during the Dosimetry Course prior to Radioimmunotherapy.

Using the Kaplan Meier method, estimate of the overall survival (OS) of patients with recurrent medulloblastoma treated with the study regimen. OS is defined as the interval of time between enrollment on the study and the minimum date of death due to any cause or date of last follow-up.

All recurrent ependymoma patients must be screened for B7H3 reactivity to be eligible for treatment on this study. B7H3 reactivity in pre-treatment formalin-fixed and paraffin-embedded tumor tissue will be assessed by IHC performed in a CLIA-certified lab. Patients whose tumors meet the reactivity criteria will be counted towards this percentage over the total number of patients who were screened.

Using the Kaplan Meier method, estimate of EFS of patients with recurrent ependymoma following incorporation of intraOmmaya 131I-omburtamab treatment. EFS is defined as the interval of time between enrollment on the study and the minimum date of documentation of progressive disease, death due to any cause, subsequent malignancy or date of last follow-up.

Using the Kaplan Meier method, estimate OS of patients with recurrent ependymoma following incorporation of intraOmmaya 131I-omburtamab treatment. OS is defined as the interval of time between enrollment on the study and the minimum date of death due to any cause or date of last follow-up.

To assess the distribution of 131I-omburtamab, Recurrent Ependymoma patients will receive one dosimetry dose (2 mCi) of cRIT 131I-omburtamab with three serial nuclear medicine scintigraphy using SPECT during the Dosimetry Course (1 week in length) prior to receiving the therapeutic dose. Organ dosimetry will be analyzed for whole body and regions of interest (ROI) and calculated based on nuclear imaging scans by whole-body planar gamma camera scans. ROIs in each planar dataset will be defined at each time point if signal is visibly above the immediate background. The mean absorbed radiation dose in CSF and whole blood will be estimated via imaging-based estimation (CSF).

Number of patients in the combined cohort (Recurrent Medulloblastoma and Ependymoma) who received at least 1 dose of 131I-omburtamab and experienced Adverse Events that were deemed at least possibly related to 131I-omburtamab will be reported by AE category as Assessed by CTCAE v5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma	NCT04743661	Recurrent Medul... Recurrent Epend...	Irinotecan Temozolomide Bevacizumab Omburtamab I-13... Liothyronine SSKI Dexamethasone Antipyretic Antihistamine anti-emetics	- 21 Years	Pediatric Brain Tumor Consortium
131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma	NCT04743661	Recurrent Medul... Recurrent Epend...	Irinotecan Temozolomide Bevacizumab Omburtamab I-13... Liothyronine SSKI Dexamethasone Antipyretic Antihistamine anti-emetics	- 21 Years	Pediatric Brain Tumor Consortium

Spots Global Cancer Trial Database for antipyretic

Every month we try and update this database with for antipyretic cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for antipyretic

Every month we try and update this database with for antipyretic cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for antipyretic cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.