Background: Trans sodium crocetinate (TSC) was developed to increase tissue oxygenation. Since hypoxia may enhance radiation resistance, we tested TSC along with radiation therapy (RT) in GBM in a Phase I/II trial. 59 patients received TSC in an open GBM clinical trial together with TMZ and RT (www.clinicaltrials.gov , NCT01465347). Although final data for the first 2 years will not be available until late summer 2015, this abstract discusses results from 18 clinical sites which are available at 21 months. Methods: 59 patients with newly diagnosed GBM were enrolled between Jan. 2012 and March 2013 into a Phase I/II trial. All patients received standard of care RT and TMZ. In the Phase I portion of the trial TSC was initially administered 3x/week at half-dose to 3 patients prior to RT. Subsequently, 6 additional patients received full dose TSC for 6 weeks in combination with RT. No dose-limiting toxicities were identified in the 9 patients on the Phase I portion of the trial. Fifty additional patients were enrolled in the Phase II trial at full dose TSC in combination with TMZ and RT. Four weeks after completion of RT, all patients resumed TMZ for 5 days every 4 weeks, but no further TSC was administered. All patients were followed with bi-monthly neurologic exams, MRI’s, KPS scores and Quality of Life questionnaires. Results: At a minimum of 21 months follow-up since the diagnosis of GBM: Radiologic Response: Pseudo progression occurred in numerous patients. Complete responses were observed in 10% of patients. Survival: Overall Survival: 38.2%. Survival did not correlate with initial tumor resection: 6/15 patients with original complete resection alive at 21 months and 8/15 biopsy-only patients. Quality Of Life: Both KPS scores and questionnaires indicate continued high QOL. Safety: Excellent patient toleration of dosing TSC with TMZ. Conclusions: TSC was well tolerated in combination with RT and TMZ. Our data at a minimum follow-up of 21 months suggest that TSC may promote radio-sensitization since there was a large incidence of pseudo-progression, with complete tumor regression in about 10% of patients and Overall Survival of 38.2%, This is one of the first demonstrations that a type of oxygen radio-sensitizer can be of benefit, being possible through the novel mechanism of TSC. Clinical trial information: NCT01465347