RESULTS OF PHASE 1 CLINICAL TRIAL OF HIGH DOSES OF SELENO-L-METHIONINE (SLM) IN SEQUENTIAL COMBINATION WITH AXITINIB IN PREVIOUSLY TREATED AND RELAPSED CLEAR CELL RENAL CARCINOMA (CCRCC) PATIENTS

630Background: The overexpression of hypoxia induced factor (HIF) 1a/2a in ccRCC leads to up-regulation of vascular endothelial growth factor (VEGF) that results in increased angiogenesis, tumor metastasis, and treatment resistance. Using several preclinical xenograft models, it has been demonstrated that therapeutic doses and schedules of the selenium-containing molecules, seleno-L-methionine (SLM) and methylselenocysteine (MSC) caused enhanced degradation of HIF1α/2α, down-regulation of oncogenic miRNA-210 and 155, up-regulation tumor suppressor miRNA-664 and LET-7b, and stabilization of tumor vasculature, yielding higher tumor drug uptake and protection from toxic side effects when combined with chemotherapeutic and VEGF-targeted agents. Methods: This is a phase I (3+3 design) dose finding trial of SLM (2500, 3000 or 4000 µg) given orally twice daily for 14 days, followed by once a day in combination with the standard dose of axitinib to patients with metastatic RCC. Primary endpoint is safety, seconda...