Evaluating Atovaquone with Radiation Therapy in Children and Young Adults Aged 2 to 25 with High-Grade and Diffuse Midline Brain Tumors

What this Trial Is About

Researchers are evaluating the safety and tolerability of atovaquone combined with standard radiation therapy for pediatric patients newly diagnosed with high-grade glioma, diffuse midline glioma, or diffuse intrinsic pontine glioma. The study also assesses longer-term atovaquone treatment safety in children and young adults with relapsed or progressive high-grade glioma, diffuse midline glioma, diffuse intrinsic pontine glioma, or medulloblastoma. Atovaquone is an FDA-approved antiparasitic drug being repurposed to target cancer cells, especially those resistant to current therapies. Participants receive atovaquone oral suspension with meals. Children aged 13 years and older get 750 mg twice daily, while those aged 2 to 12 years receive 30 mgkg once daily, up to 1500 mg maximum. Newly diagnosed patients start atovaquone 2 weeks before radiation therapy, continuing approximately 6 weeks alongside radiation. Patients with relapse or progression or those who completed radiation without prior atovaquone may receive the drug for up to 6 months if tolerated. Radiation involves MRI-guided proton therapy in daily fractions totaling 54-60 Gy. During the study, participants are monitored for drug-related toxicities at baseline and after treatment periods of 10 weeks or up to 7 months, depending on the group. Researchers assess progression-free survival, overall survival, and tumor response. Evaluations include organ and marrow function tests, seizure stability checks, and liver function monitoring. The study lasts until October 2027 and aims to expand treatment options for challenging pediatric brain tumors using this combination therapy.

Atovaquone Combined With Radiation in Children With Malignant Brain Tumors