Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)

Introduction The standard of care for stage III colon cancer is 3 or 6 months of double-drug regimen chemotherapy following radical surgery. However, patients with positive circulating tumour DNA (ctDNA) exhibit a high risk of recurrence risk even if they receive standard adjuvant chemotherapy. The...

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Main Authors: Jun Huang, Rui Fan, Ziqiang Wang, Meng Qiu, Jiahao Zhou, Zikai Zhou, Xiangbing Deng, Qingbin Wu
Format: Article
Language:English
Published: BMJ Publishing Group 2025-01-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/1/e090394.full
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author Jun Huang
Rui Fan
Ziqiang Wang
Meng Qiu
Jiahao Zhou
Zikai Zhou
Xiangbing Deng
Qingbin Wu
author_facet Jun Huang
Rui Fan
Ziqiang Wang
Meng Qiu
Jiahao Zhou
Zikai Zhou
Xiangbing Deng
Qingbin Wu
author_sort Jun Huang
collection DOAJ
description Introduction The standard of care for stage III colon cancer is 3 or 6 months of double-drug regimen chemotherapy following radical surgery. However, patients with positive circulating tumour DNA (ctDNA) exhibit a high risk of recurrence risk even if they receive standard adjuvant chemotherapy. The potential benefit of intensified adjuvant chemotherapy, oxaliplatin, irinotecan, leucovorin and fluoropyrimidine (FOLFOXIRI), for ctDNA-positive patients remains to be elucidated.Methods and analysis This multicentre phase II randomised controlled trial aims to investigate the utility of ctDNA in monitoring chemosensitivity and to preliminarily assess whether intensified chemotherapy with FOLFOXIRI can increase ctDNA clearance and improve survival outcomes. A total of 60 eligible patients with stage III colon cancer exhibiting postoperatively positive ctDNA before and after two cycles of oxaliplatin and capecitabine (XELOX) will be randomly assigned to continue five additional cycles of XELOX (control arm) or switch to eight cycles of FOLFOXIRI (experimental arm). This sequential approach is designed to escalate treatment for patients with persistent ctDNA positivity while avoiding overtreatment in those who may respond well to standard chemotherapy. The primary endpoint is the change in ctDNA concentration, defined as the difference between the ctDNA concentration measured after two cycles of XELOX and after the completion or termination of chemotherapy. Secondary endpoints include the ctDNA clearance rate, 2-year disease-free survival, distant metastasis-free survival, chemotherapy-related side effects and quality of life.Ethics and dissemination This trial has been approved by the Ethics Committee of the West China Hospital, Sichuan University (approval number: 20231998). The findings will be disseminated through peer-reviewed publications and presentations at scientific conferences.Trial registration number ClinicalTrials.gov (NCT06242418, registered on 27 January 2024).
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spelling doaj-art-0554d0a2825849ad92d27e624c4824a32025-01-06T18:30:09ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-090394Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)Jun Huang0Rui Fan1Ziqiang Wang2Meng Qiu3Jiahao Zhou4Zikai Zhou5Xiangbing Deng6Qingbin Wu71 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China2 Genecast Biotechnology Co Ltd, Jiangsu, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China1 Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, ChinaIntroduction The standard of care for stage III colon cancer is 3 or 6 months of double-drug regimen chemotherapy following radical surgery. However, patients with positive circulating tumour DNA (ctDNA) exhibit a high risk of recurrence risk even if they receive standard adjuvant chemotherapy. The potential benefit of intensified adjuvant chemotherapy, oxaliplatin, irinotecan, leucovorin and fluoropyrimidine (FOLFOXIRI), for ctDNA-positive patients remains to be elucidated.Methods and analysis This multicentre phase II randomised controlled trial aims to investigate the utility of ctDNA in monitoring chemosensitivity and to preliminarily assess whether intensified chemotherapy with FOLFOXIRI can increase ctDNA clearance and improve survival outcomes. A total of 60 eligible patients with stage III colon cancer exhibiting postoperatively positive ctDNA before and after two cycles of oxaliplatin and capecitabine (XELOX) will be randomly assigned to continue five additional cycles of XELOX (control arm) or switch to eight cycles of FOLFOXIRI (experimental arm). This sequential approach is designed to escalate treatment for patients with persistent ctDNA positivity while avoiding overtreatment in those who may respond well to standard chemotherapy. The primary endpoint is the change in ctDNA concentration, defined as the difference between the ctDNA concentration measured after two cycles of XELOX and after the completion or termination of chemotherapy. Secondary endpoints include the ctDNA clearance rate, 2-year disease-free survival, distant metastasis-free survival, chemotherapy-related side effects and quality of life.Ethics and dissemination This trial has been approved by the Ethics Committee of the West China Hospital, Sichuan University (approval number: 20231998). The findings will be disseminated through peer-reviewed publications and presentations at scientific conferences.Trial registration number ClinicalTrials.gov (NCT06242418, registered on 27 January 2024).https://bmjopen.bmj.com/content/15/1/e090394.full
spellingShingle Jun Huang
Rui Fan
Ziqiang Wang
Meng Qiu
Jiahao Zhou
Zikai Zhou
Xiangbing Deng
Qingbin Wu
Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
BMJ Open
title Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
title_full Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
title_fullStr Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
title_full_unstemmed Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
title_short Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial)
title_sort value of ctdna in surveillance of adjuvant chemosensitivity and regimen adjustment in stage iii colon cancer a protocol for phase ii multicentre randomised controlled trial revise trial
url https://bmjopen.bmj.com/content/15/1/e090394.full
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