306 - Preliminary Results of a Phase I Study of Pharmacological Ascorbate (P-AscH–) with Gemcitabine Chemoradiotherapy in Pancreatic Cancer

Abstract

P-AscH– radiosensitizes pancreatic cancer (PDAC) in vitro and in vivo. The purpose of this Phase I trial is to determine the safety and tolerability of P-AscH- when combined with gemcitabine and radiation. Patients with locally advanced PDAC who were to undergo gemcitabine and radiotherapy were enrolled (Clinical Trials.gov NCT0152890). Patients were given P-AscH– (50-100 g/daily), 5 days/week and Gemcitabine as prescribed per standard of care guidelines. Intensity modulated radiation therapy was also administered at either 50.4 Gy in 28 fractions or 50 Gy in 25 fractions. The primary endpoints were safety and tolerability of P-AscH– other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. Since June, 2014, 14 patients have enrolled and 11 have completed therapy. Both 75 gram and 100 gram infusions achieved plasma ascorbate levels of 20 mM. The adverse event most commonly attributable to P-AscH– was dry mouth during infusion. No other adverse events were observed to be greater in intensity or frequency than with gemcitabine and radiation alone. Grade 3 or greater adverse events were hematologic in nature which occurred in all patients to varying severity. One P-AscH–-related toxicity was reported with non-cardiac chest pain which did not alter ongoing treatment. Common grade 1 and 2 adverse events included chills, abdominal pain, dry mouth, fatigue, nausea, vomiting, and thrombocytopenia, all in similar frequency and intensity to chemoradiotherapy alone. Progression Free and overall survival is 10.8 months and 13.1 months, respectively, compared to 6.0 months and 11.1 months, for historical controls. Our preliminary results demonstrate that P-AscH– in combination with gemcitabine/radiation is safe and tolerable.