CTNI-30. A PHASE 2 DOUBLE-BLIND, RANDOMIZED, PROSPECTIVE, PLACEBO CONTROLLED STUDY OF NANO₂TM COMBINED WITH RADIATION AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA: RESTORE

Abstract INTRODUCTION Glioblastoma (GBM) commonly has extensive hypoxic regions, possibly due to thrombosis from tumor-produced pro-coagulant factors. Radiation-induced cell death relies on oxygen free radicals and oxygen fixation of DNA-strand breaks. In the absence of oxygen tumor cells can repair the DNA strand breaks leading to treatment resistance. Hypoxic cells also exhibit chemoresistance due to decreased drug efficacy, limited drug diffusion, and poor delivery to distant cells. This study hypothesizes that increasing oxygen delivery to hypoxic GBM tissue using NanO₂ (2% w/v dodecafluoropentane emulsion) infusion will enhance the effectiveness of radiation therapy (RT) and chemotherapy (CT). METHODS Patients diagnosed with GBM per CNS5-WHO criteria receive standard chemoradiation: 30 fractions of focal RT with 60 Gy, delivered as 2 Gy fractions five days per week for six weeks with concurrent oral TMZ at 75 mg/m²/day for six weeks. Patients are randomized in a 1:2 ratio to receive either a placebo (0.9% Sodium Chloride) or NanO₂ infusion administered immediately prior to each RT dose. Patients continuously breathe oxygen during infusion and RT. Following six weeks of RT with temozolomide, patients have a four-week break before starting adjuvant temozolomide. RESULTS Ten patients have been enrolled in the RESTORE trial. Seven continue to be followed through maintenance treatment and long term follow up. There have been 23 non-hematologic adverse events described as CTCAE severity grade 3 and above. Grade 4, hematologic toxicity occurred in two patients, with one patient experiencing prolonged pancytopenia necessitating hematologic support and discontinuation of temozolomide. Two patients discontinued therapy due to early tumor progression. CONCLUSION This study is ongoing, assessing the safety and potential efficacy of NanO₂ in improving treatment outcomes for GBM by enhancing oxygen delivery to hypoxic tumor regions.