Phase I study of plerixafor and bevacizumab in recurrent high-grade glioma.

TPS2080 Background: Although anti-angiogenic therapy for high-grade glioma is promising, responses are not durable. The SDF-1/CXCR4 axis may help mediate resistance to VEGFR inhibition. Plerixafor is a reversible CXCR4 inhibitor that has demonstrated growth inhibition in glioblastoma xenografts. Methods: We are conducting a Phase I study to determine the safety and tolerability of plerixafor in combination with bevacizumab in patients with recurrent HGG. In Part 1 of the study, a 3 x 3 dose escalation design to a maximum planned dose level of plerixafor 320 µg/kg on Days 1-21 and bevacizumab 10 mg/kg on Days 1 and 15 of each 28 day cycle was used. DLTs were determined during the initial 4 weeks of therapy and included drug-related Grade ≥ 3 non-hematologic toxicities and Grade ≥ 4 hematologic toxicities. Part 2 of the study is a surgical study to determine if plerixafor penetrates tumor tissue. Results: Part 1 of the study has been completed with 23 patients enrolled. Part 2 of the study is now open with ...