Study protocol of the Asian XELIRIrnProjecT (AXEPT): a multinational, randomized,rnnon‑inferiority, phase III trial of second‑linernchemotherapy for metastatic colorectal cancer,rncomparing the efficacy and safety of XELIRIrnwith or without bevacizumab versus FOLFIRIrnwith or without bevacizumab

摘要

Background:Capecitabine and irinotecan combination therapy (XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer (mCRC). Recently, in the Association of Medical Oncology of the German Cancer Society (AIO) 0604 trial, tri‑weekly XELIRI plus bevacizumab, with reduced doses of irinotecan (200mg/m2 on day 1) and capecitabine (1600mg/m2 on days 1–14), repeated every 3weeks, has shown favorable tolerability and effcacy which were comparable to those of capecitabine and oxaliplatin (XELOX) plus bevacizumab. The doses of capecit‑abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab (BIX) as second‑line chemotherapy was well tolerated and had promising effcacy in Japanese patients. Methods:The Asian XELIRI ProjecT (AXEPT) is an East Asian collaborative, open‑labelled, randomized, phase III clinical trial which was designed to demonstrate the non‑inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI (5‑lfuorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second‑line chemo‑therapy for patients with mCRC. Patients with 20years of age or older, histologically conifrmed mCRC, Eastern Coop‑erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the ifrst‑line regimen will be eligible. Patients will be randomized (1:1) to receive standard FOLFIRI with or with‑out bevacizumab (5mg/kg on day 1), repeated every 2weeks (FOLIRI arm) or XELIRI with or without bevacizumab (7.5mg/kg on day 1), repeated every 3weeks (XELIRI arm). A total of 464 events were estimated as necessary to show non‑inferiority with a power of 80% at a one‑sided α of 0.025, requiring a target sample size of 600 patients. The 95% conifdence interval (CI) upper limit of the hazard ratio was pre‑speciifed as less than 1.3. Conclusion:The Asian XELIRI ProjecT is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second‑line treatment option of mCRC.