title: Study protocol of the Asian XELIRI ProjecT (AXEPT): a multinational, randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer, comparing the efficacy and safety of XELIRI with or without bevacizumab versus FOLFIRI with or without bevacizumab.
abstract: 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 (200 mg/m2on day 1) and capecitabine (1600 mg/m2on days 1-14), repeated every 3 weeks, has shown favorable tolerability and efficacy which were comparable to those of capecitabine and oxaliplatin (XELOX) plus bevacizumab. The doses of capecitabine 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 efficacy in Japanese patients.
  
  
  
  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-fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second-line chemotherapy for patients with mCRC. Patients with 20 years of age or older, histologically confirmed mCRC, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and disease progression or intolerance of the first-line regimen will be eligible. Patients will be randomized (1:1) to receive standard FOLFIRI with or without bevacizumab (5 mg/kg on day 1), repeated every 2 weeks (FOLIRI arm) or XELIRI with or without bevacizumab (7.5 mg/kg on day 1), repeated every 3 weeks (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% confidence interval (CI) upper limit of the hazard ratio was pre-specified as less than 1.3.
  
  
  
  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. Trial registration ClinicalTrials.gov NCT01996306. UMIN000012263.
authors.affiliation: Gastrointestinal Cancer Center, Sano Hospital, Hyogo, 655-0031, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kotaka
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, South Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Department of Surgical Specialties, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, Tokyo, 113-0033, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nozawa
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, 113-8677, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, 110-744, South Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Gastrointestinal Oncology, The First People's Hospital of Foshan, Foshan, Guangdong, 528000, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 120-752, South Korea.
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, P. R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, 519-809, South Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Digestive Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang HospitalSeoul National University College of Medicine, Seongnam, 463-707, South Korea.
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: International Drug Development Institute, Louvain-La-Neuve, 1340, Belgium.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Buyse
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, 138-736, South Korea.
authors.forename: Baek-Yeol
authors.initials: BY
authors.lastname: Ryoo
authors.affiliation: Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100-142, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Tokai Central Hospital, Kakamigahara, 504-8601, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, 138-736, South Korea. twkimmd@amc.seoul.kr.
authors.forename: Tae Won
authors.identifier: 0000-0001-9522-1997
authors.initials: TW
authors.lastname: Kim
mesh_terms: D006801:Humans; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001208:Asia; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000556:secondary; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D007390:International Agencies; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D009367:Neoplasm Staging; D011379:Prognosis; D016879:Salvage Therapy; D000074099:Equivalence Trials as Topic
chemical_list: D000068258:Bevacizumab; D002166:Camptothecin; D000069287:Capecitabine; D005472:Fluorouracil; D000077146:Irinotecan; D002955:Leucovorin
keywords: Bevacizumab; Metastatic colorectal cancer; Randomized phase III clinical trial; Second-line therapy; XELIRI