A phase I study of chemo-radiotherapy with plerixafor for newly diagnosed glioblastoma (GB).

2068Background: Preclinical studies indicate that local recurrence after radiotherapy (RT) of Glioblastoma is dependent on recovery of tumor vasculature following RT via hypoxia-driven SDF-1 (CXCL12) secretion. We hypothesize that blocking the CXCL12/CXCR4 axis would improve local control. Methods: Newly diagnosed Glioblastoma patients were recruited to this Phase I study of a 4 week intravenous infusion of Plerixafor (Mozobil), a CXCR4 antagonist, with concurrent Temozolomide (TMZ) and radiation therapy. Three patients were treated with Plerixafor at 8.3 µg/kg/hr and six patients at 16.6 µg/kg/hr, while being monitored for dose limiting toxicities (DLTs) including grade ≥ 3 hematologic or non-hematologic adverse events. Patients underwent dynamic susceptibility contrast perfusion MRI (DSC-MRI) for quantification of relative cerebral blood volume (rCBV) values by region-of-interest analysis. Pharmacokinetic (PK) analysis of Plerixafor plasma levels were collected. Results: Since August 2014, 9 patients co...