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.

Masahito Kotaka, Ruihua Xu, Kei Muro, Young Suk Park, Satoshi Morita, Satoru Iwasa, Hiroyuki Uetake, Tomohiro Nishina, Hiroaki Nozawa, Hiroshi Matsumoto, Kentaro Yamazaki, Sae-Won Han, Wei Wang, Joong Bae Ahn, Yanhong Deng, Sang-Hee Cho, Yi Ba, Keun-Wook Lee, Tao Zhang, Taroh Satoh, Marc E Buyse, Baek-Yeol Ryoo, Lin Shen, Junichi Sakamoto, Tae Won Kim

Journal: Chinese journal of cancer 2017;35(1):102

PMID: 28007025

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Abstract

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 (200 mg/m on day 1) and capecitabine (1600 mg/m on 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.

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-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.

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. Trial registration ClinicalTrials.gov NCT01996306. UMIN000012263.

Address: Gastrointestinal Cancer Center, Sano Hospital, Hyogo, 655-0031, Japan.; 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.; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan.; Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, South Korea.; Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan.; Department of Surgical Specialties, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.; Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan.; Department of Surgical Oncology, The University of Tokyo, Tokyo, 113-0033, Japan.; Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, 113-8677, Japan.; Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.; Department of Internal Medicine, Seoul National University Hospital, Seoul, 110-744, South Korea.; Department of Gastrointestinal Oncology, The First People's Hospital of Foshan, Foshan, Guangdong, 528000, P. R. China.; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 120-752, South Korea.; Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, P. R. China.; Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, 519-809, South Korea.; Department of Digestive Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P. R. China.; Department of Internal Medicine, Seoul National University Bundang HospitalSeoul National University College of Medicine, Seongnam, 463-707, South Korea.; Department of Medical Oncology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P. R. China.; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.; International Drug Development Institute, Louvain-La-Neuve, 1340, Belgium.; Department of Oncology, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, 138-736, South Korea.; Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100-142, P. R. China.; Tokai Central Hospital, Kakamigahara, 504-8601, Japan.; Department of Oncology, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, 138-736, South Korea. [email protected].

DOI: 10.1186/s40880-016-0166-3

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MeSH Terms: Antineoplastic Combined Chemotherapy Protocols, Asia, Bevacizumab, Camptothecin, Capecitabine, Colorectal Neoplasms, Fluorouracil, Follow-Up Studies, Humans, International Agencies, Irinotecan, Leucovorin, Neoplasm Staging, Prognosis, Salvage Therapy