In 2009, Kieran et al. [121] performed a traditional 3+3 phase I study in children with refractory brain tumors to determine MTD and the safety of semaxinib (SU5416), a small molecule tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 and 2 (VEGFR1-2) [122]. This evidence concerns the gene FLT1 and brain neoplasm.