Researchers are recruiting pediatric medulloblastoma patients for a novel use of difluoromethylornithine (DFMO) to prevent relapse.

The multisite study, sponsored by the Beat Childhood Cancer Consortium and led by Michael Angelo C. Huang, M.D., pediatric neuro-oncologist at Norton Children’s Cancer Institute, affiliated with the UofL School of Medicine, looks at whether DFMO offers a new and safe option as extended maintenance therapy for molecular high risk/very high risk medulloblastoma as well refractory or relapsed cases who have a small amount of stable residual disease..

Dr. Huang is the co-director of the Norton Children’s Cancer Institute Neuro-oncology Program.

“This is an exciting trial for a group of patients who currently have a poor prognosis,” said Dr. Huang, principal investigator and study chair for the 13-site clinical trial.

While there are specific criteria for patients, they must have been less than 21 years old at diagnosis with a confirmed medulloblastoma that is molecular high risk, molecular very high risk. Relapsed/refractory patients are also eligible but would need to receive conventional salvage therapy first and have non-bulky residual disease that is stable.

Overall survival for noninfant childhood medulloblastoma (ages 3 to 17) is 75% to 90%.Medulloblastoma patients with molecular high-risk or very high-risk features have more dismal outcomes. Survival drops to < 50% in patients with molecular high risk/very high risk medulloblastoma.

The non-randomized, single arm, open-label, Phase II trial (NCT04696029) is currently in the recruitment stage. Patients will receive DMFO every day for two years. Subjects will be evaluated in three cohorts: molecular high risk, molecular very high risk, and relapsed/refractory.

Twelve patients have been enrolled to date. A total of 118 subjects will be enrolled across the three cohorts.

The study has a five-year follow-up and will evaluate DFMO as a single agent in preventing relapse, based on the two-year progression survival rate, comparing against relevant historical controls. The study also will look at overall survival at 2 years.

Maintenance DFMO treatment is now FDA approved for high-risk neuroblastoma, another aggressive pediatric neural type cancer, after demonstrating improved cancer-free and overall survival in heavily pretreated patients. DFMO is able to target a specific cancer pathway shared by both cancer types.

DFMO, also called eflornithine, is a synthetic analog of the amino acid ornithine. Instead of targeting the tumor cells directly, it targets ornithine decarboxylase (ODC), the rate-limiting enzyme involved with polyamine biosynthesis. Polyamines facilitate cancer cell growth and development, including renewal of cancer stem cells

Current treatment for medulloblastoma is maximal safe resection, followed by radiation and chemotherapy.

Medulloblastoma is rare, affecting between 350 and 500 children and adults in the United States each year, but accounts for a fifth of all pediatric brain tumors. Peak age at diagnosis is 4 to 5 years old. Affected children generally present with coordination or balance symptoms and/or hydrocephalus.