NCT06624371

Atovaquone Combined With Radiation in Children With Malignant Brain Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 2 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma/diffuse midline glioma/diffuse intrinsic pontine glioma (pHGG/DMG/DIPG). The secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of RT and before progression.

Detailed description

Atovaquone, an FDA-approved antiparasitic drug, is being explored as a potential treatment for certain cancers, particularly leukemia and pediatric brain tumors like high-grade gliomas. Since Atovaquone's safety and dosage are already established, repurposing it for cancer treatment is cost-effective. Research shows that Atovaquone can inhibit a protein called STAT3, which is involved in cancer cell survival and immune response suppression. By doing this, it may enhance the effectiveness of radiation therapy, especially in tumors with low oxygen levels. In animal studies and early clinical trials, Atovaquone has shown promise in reducing tumor size and improving survival rates. For pediatric brain tumors, which often resist standard treatments, Atovaquone's ability to cross the blood-brain barrier could make it particularly valuable. Ongoing clinical trials are examining its effects in combination with radiation therapy for treating newly diagnosed high-grade gliomas and relapsed medulloblastomas. Overall, Atovaquone's repurposing could lead to new, effective treatment options for difficult-to-treat cancers in children.

Conditions

• High-grade Glioma
• Medulloblastoma
• Diffuse Intrinsic Pontine Glioma
• Diffuse Midline Glioma, H3 K27M-Mutant

Interventions

Type	Name	Description
DRUG	Atovaquone	Atovaquone oral suspension (750 mg/5mL) will be administered with meals on an outpatient basis. Patients 13 years and older will receive atovaquone 750 mg PO BID, the standard pediatric dosing for Pneumocystis Jirovecii Pneumonia (PJP) prevention and treatment. For those aged 2-12 years, atovaquone will be dosed at 30mg/kg once daily. The maximum dose for children under 12 will be 1500 mg.
RADIATION	Radiation Therapy	54-60 Gy in 1.8 Gy daily fractions of MRI-guided proton radiotherapy using intensity-modulated pencil-beam scanning technology to match the target will be used.

Timeline

• Start date: 2025-03-28
• Primary completion: 2027-10-01
• Completion: 2027-10-01
• First posted: 2024-10-03
• Last updated: 2025-07-22

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study