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 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...
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BMC
2016-12-01
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| Series: | Chinese Journal of Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s40880-016-0166-3 |
| _version_ | 1828255566823161856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Masahito Kotaka |
| collection | DOAJ |
| description | 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/m2 on day 1) and capecitabine (1600 mg/m2 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 |
| first_indexed | 2024-04-13T02:16:28Z |
| format | Article |
| id | doaj.art-eb63a8e296ca4e8aa490324d9158a4b6 |
| institution | Directory Open Access Journal |
| issn | 1944-446X |
| language | English |
| last_indexed | 2024-04-13T02:16:28Z |
| publishDate | 2016-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Journal of Cancer |
| spelling | doaj.art-eb63a8e296ca4e8aa490324d9158a4b62022-12-22T03:07:09ZengBMCChinese Journal of Cancer1944-446X2016-12-013511810.1186/s40880-016-0166-3Study 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 bevacizumabMasahito Kotaka0Ruihua Xu1Kei Muro2Young Suk Park3Satoshi Morita4Satoru Iwasa5Hiroyuki Uetake6Tomohiro Nishina7Hiroaki Nozawa8Hiroshi Matsumoto9Kentaro Yamazaki10Sae-Won Han11Wei Wang12Joong Bae Ahn13Yanhong Deng14Sang-Hee Cho15Yi Ba16Keun-Wook Lee17Tao Zhang18Taroh Satoh19Marc E. Buyse20Baek-Yeol Ryoo21Lin Shen22Junichi Sakamoto23Tae Won Kim24Gastrointestinal Cancer Center, Sano HospitalState Key Laboratory of Oncology in South China, Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto UniversityGastrointestinal Medical Oncology Division, National Cancer Center HospitalDepartment of Surgical Specialties, Graduate School, Tokyo Medical and Dental UniversityDepartment of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer CenterDepartment of Surgical Oncology, The University of TokyoDepartment of Surgery, Tokyo Metropolitan Komagome HospitalDivision of Gastrointestinal Oncology, Shizuoka Cancer CenterDepartment of Internal Medicine, Seoul National University HospitalDepartment of Gastrointestinal Oncology, The First People’s Hospital of FoshanDepartment of Internal Medicine, Yonsei University College of MedicineDepartment of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Hematology-Oncology, Chonnam National University Medical SchoolDepartment of Digestive Oncology, Tianjin Medical University Cancer Institute and HospitalDepartment of Internal Medicine, Seoul National University Bundang HospitalSeoul National University College of MedicineDepartment of Medical Oncology, Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka UniversityInternational Drug Development InstituteDepartment of Oncology, Asan Medical Center, University of Ulsan Collage of MedicineDepartment of Gastrointestinal Oncology, Peking University Cancer Hospital & InstituteTokai Central HospitalDepartment of Oncology, Asan Medical Center, University of Ulsan Collage of MedicineAbstract 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/m2 on day 1) and capecitabine (1600 mg/m2 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. UMIN000012263http://link.springer.com/article/10.1186/s40880-016-0166-3Metastatic colorectal cancerRandomized phase III clinical trialXELIRIBevacizumabSecond-line therapy |
| spellingShingle | 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 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 Chinese Journal of Cancer Metastatic colorectal cancer Randomized phase III clinical trial XELIRI Bevacizumab Second-line therapy |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Metastatic colorectal cancer Randomized phase III clinical trial XELIRI Bevacizumab Second-line therapy |
| url | http://link.springer.com/article/10.1186/s40880-016-0166-3 |
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