131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma

Summary

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.

Conditions

• Recurrent Medulloblastoma
• Recurrent Ependymoma

Interventions

DRUG

Irinotecan

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.

DRUG

Temozolomide

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.

DRUG

Bevacizumab

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.

DRUG

Omburtamab I-131

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.

DRUG

Liothyronine

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.

DRUG

SSKI

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.

DRUG

Dexamethasone

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.

DRUG

Antipyretic

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.

DRUG

Antihistamine

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.

DRUG

anti-emetics

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Memorial Sloan Kettering Cancer Center

  collaborator OTHER

• Y-mAbs Therapeutics

  collaborator INDUSTRY

• Pediatric Brain Tumor Consortium

  lead NETWORK

Principal Investigators

• Matthias Karajannis, MD, MS · Memorial Sloan Kettering Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-04-04

Primary Completion

2026-03-31

Completion

2027-09-30

FDA Drug

Yes

Countries

• United States

Study Locations