Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial
Abstract Background Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor...
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-019-3917-z |
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| author | Cheng-Jen Ma Tsung-Kun Chang Hsiang-Lin Tsai Wei-Chih Su Ching-Wen Huang Yung-Sung Yeh Yu-Tang Chang Jaw-Yuan Wang |
| author_facet | Cheng-Jen Ma Tsung-Kun Chang Hsiang-Lin Tsai Wei-Chih Su Ching-Wen Huang Yung-Sung Yeh Yu-Tang Chang Jaw-Yuan Wang |
| author_sort | Cheng-Jen Ma |
| collection | DOAJ |
| description | Abstract Background Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC. Methods A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded. Discussion Dose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC. Trial registration ClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019. |
| first_indexed | 2024-12-16T12:43:23Z |
| format | Article |
| id | doaj.art-606735c6face44e4ae00c62351bed773 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-16T12:43:23Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-606735c6face44e4ae00c62351bed7732022-12-21T22:31:21ZengBMCTrials1745-62152019-12-012011910.1186/s13063-019-3917-zRegorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trialCheng-Jen Ma0Tsung-Kun Chang1Hsiang-Lin Tsai2Wei-Chih Su3Ching-Wen Huang4Yung-Sung Yeh5Yu-Tang Chang6Jaw-Yuan Wang7Division of Digestive and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityAbstract Background Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC. Methods A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded. Discussion Dose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC. Trial registration ClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019.https://doi.org/10.1186/s13063-019-3917-zRegorafenibUGT1A1FOLFIRIDose escalationMetastatic colorectal cancer |
| spellingShingle | Cheng-Jen Ma Tsung-Kun Chang Hsiang-Lin Tsai Wei-Chih Su Ching-Wen Huang Yung-Sung Yeh Yu-Tang Chang Jaw-Yuan Wang Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial Trials Regorafenib UGT1A1 FOLFIRI Dose escalation Metastatic colorectal cancer |
| title | Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial |
| title_full | Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial |
| title_fullStr | Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial |
| title_full_unstemmed | Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial |
| title_short | Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial |
| title_sort | regorafenib plus folfiri with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1a1genotyping in previous treated metastatic colorectal cancer patients study protocol for a randomized controlled trial |
| topic | Regorafenib UGT1A1 FOLFIRI Dose escalation Metastatic colorectal cancer |
| url | https://doi.org/10.1186/s13063-019-3917-z |
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