A Phase I Feasibility Trial of Tumor Treating Fields Therapy with Temozolomide and Bevacizumab in Pediatric High-Grade Glioma

Background Pediatric high-grade glioma (HGG) has a poor prognosis with limited therapeutic options. Tumor Treating Fields (TTFields) therapy, delivered via Optune Gio, improves outcomes in adult glioblastoma, but pediatric data remain limited. This phase I study evaluated the safety and tolerability of TTFields combined with temozolomide and bevacizumab in pediatric HGG. Methods In this prospective, open-label, single-arm phase I safety study, patients aged ≥5 and ≤21 years with newly diagnosed or recurrent supratentorial high-grade glioma (HGG) received TTFields therapy (200 kHz, ≥18 hours/day) with temozolomide and bevacizumab in 28-day cycles. The primary endpoint was the occurrence of protocol-defined treatment-related dose-limiting toxicities (DLTs) during the first two cycles (56 days). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and quality of life (QOL). Results Seven patients (ages 13–21; five newly diagnosed, two recurrent glioblastoma) were enrolled, with six evaluable for safety. No protocol-defined treatment-related DLTs occurred during the 56-day safety evaluation period. Grade 3–4 adverse events were consistent with expected chemotherapy-related toxicities. Device-related toxicities were limited to manageable dermatologic reactions. Among the four newly diagnosed evaluable patients, three progressed after Cycles 8–13, while one remained in remission >5 years from diagnosis. Both recurrent patients progressed after two cycles. QOL responses showed low device-related burden for most participants. One patient discontinued after Cycle 1 due to substantial QOL impact. Conclusion TTFields combined with temozolomide and bevacizumab met the protocol-defined safety threshold in pediatric HGG, with no device-related severe toxicities. These findings support further investigation of TTFields-based therapy in larger prospective studies.