Randomised Phase 3 Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer (AGOC) - INTEGRATE II

摘要: Abstract Background AGOC has a poor prognosis with limited benefits from treatments following failure of chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET KIT). INTEGRATE (phase 2) demonstrated REG effectiveness prolonging PFS pts, positive OS trend less toxicity than other trials at the same doses. was effective across all regions/subgroups, regional differences noted magnitude effect. II 3) will explore whether survival patients, Asian sub-population Methods International randomised phase III, double-blind, placebo-controlled trial 2:1 (REG:placebo)(PBO) randomisation stratification by tumour location, geographic region, prior VEGF inhibitors. Histologically confirmed evaluable metastatic or locally advanced disease refractory to/relapsed least 2 lines CT, receive best supportive care plus 160mg matched placebo orally on days 1-21 each 28 day cycle until progression prohibitive adverse events. Primary endpoint OS. Secondary endpoints: PFS, response rate, quality life, safety, identification prognostic/predictive biomarkers for study endpoints, PK geographical regions. 350 patients (50% Asia, 50 to be recruited Japan) randomized ratio provide 90% power detect hazard (HR) 0.67 2-sided α 0.05 assuming PBO median 4.5 mos. The sample size accommodates interim analysis undertaken once 2/3 required events have occurred. Results 27 ANZ, 8 Canadian, 15 Korean, 5 Taiwanese, Japanese sites been activated 106 enrolled. Remaining Japanese/US expected activate through Q1/Q2 2019.