Background

This clinical trial evaluates the efficacy of combining bevacizumab (an anti‑VEGF antibody) with standard chemotherapy in pediatric patients with relapsed or refractory high‑risk neuroblastoma. Bevacizumab blocks vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis, and is combined with temozolomide and either irinotecan or topotecan. The study was designed because survival rates for relapsed patients remain low with existing therapies, highlighting the need for novel combination regimens.

Key Design and Objectives

Phase II, randomized allocation, with treatment duration of 18–24 weeks. The primary endpoint is overall response rate (complete or partial response, CR/PR). The primary endpoint assesses tumor response observed during therapy, while secondary objectives include safety, progression‑free survival (PFS), and overall survival (OS). Bevacizumab will be added to each chemotherapy backbone (temozolomide + irinotecan, temozolomide + topotecan, etc.) for comparative evaluation.

Mechanism of Action and Differentiation

Bevacizumab is an anti‑angiogenic agent that deprives tumors of blood supply, thereby inhibiting growth. Temozolomide combined with irinotecan or topotecan provides DNA damage through alkylation and topoisomerase I inhibition, enhancing the efficacy of standard chemotherapy. Simultaneous application of these two mechanisms is expected to achieve higher tumor response rates than monotherapy.

Current Treatment Landscape and Expected Impact

Standard treatment for relapsed or refractory neuroblastoma includes high‑dose chemotherapy, radiation therapy, and immunotherapies such as dinutuximab, but overall success rates remain limited. If a bevacizumab‑containing regimen improves response rates compared with chemotherapy alone, it could broaden therapeutic options and extend patient survival. Demonstrating the feasibility of anti‑angiogenic agents like bevacizumab may also have downstream implications for developing strategies against similar tumor types.