Radioimmunotherapy for Recurrent Pediatric Brain Cancer

This trial explores a potential new treatment for children with recurring brain tumors, specifically medulloblastoma and ependymoma. It adds a special type of targeted radiation therapy (radioimmunotherapy) to existing cancer drugs, including Bevacizumab (Avastin), Irinotecan (Camptosar or CPT-11), Omburtamab I-131, and Temozolomide (Temodar or Temodal). The trial aims to determine if this combination can better manage tumor growth and improve survival rates. Children with recurring brain cancer that has not responded well to past treatments, and who have persistent MRI abnormalities or tumor cells in spinal fluid, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering hope for improved tumor growth management.

You may need to stop certain medications before joining the trial. Specifically, you cannot take enzyme-inducing antiepileptic drugs, certain herbal supplements, or medications that strongly affect liver enzymes (CYP3A4/5) within 7 days before enrollment. Check with the trial team for guidance on your specific medications.

Previous studies have tested the drugs irinotecan, temozolomide, and bevacizumab in children with brain tumors. Irinotecan was generally well-tolerated, though some patients experienced side effects such as diarrhea and low white blood cell counts. Temozolomide demonstrated a 42.5% response rate in children with brain tumors, but some encountered serious side effects like low blood cell counts. Bevacizumab appears safe for children, with manageable side effects such as high blood pressure and protein in urine.

Researchers are excited about the radioimmunotherapy approach using 131I-omburtamab because it offers a unique strategy for treating recurrent pediatric brain cancers like medulloblastoma and ependymoma. Unlike traditional chemotherapy or radiation, this treatment delivers targeted radiation directly to cancer cells by attaching a radioactive isotope, 131I, to the antibody omburtamab, which specifically targets the B7H3 protein often found on these tumors. This precise delivery method could potentially minimize damage to healthy brain tissue and improve outcomes for children with these challenging cancers. Moreover, the use of intraOmmaya administration allows the radioactive treatment to be directly introduced into the cerebrospinal fluid, targeting tumors more effectively.

In this trial, one arm will study the combination of three drugs—irinotecan, temozolomide, and bevacizumab—for children with recurring medulloblastoma, a type of brain tumor. Studies have shown that this combination can significantly lower the risk of death and effectively shrink tumors in about two-thirds of these patients. Another arm will focus on using 131I-omburtamab for patients with recurrent ependymoma. Research suggests that adding 131I-omburtamab might improve survival rates, especially for patients whose cancer is not currently active. This treatment directly targets tumor cells, aiding in the detection and treatment of returning brain tumors. Early results indicate that 131I-omburtamab may help keep patients in remission longer and is considered safe for use in these cases.⁶⁷⁸⁹¹⁰