Assaf Irene, Bregni Giacomo, Anthoine Geraldine, Aparicio Thomas, Artru Pascal, Abdelghani Meher Ben, Buyse Marc, Chibaudel Benoist, Coart Elisabeth, Diaz Marie, Evrard Camille, Geboes Karen, Ghiringhelli François, Puleo Francesco, Raimbourg Judith, Vandamme Timon, Van den Eynde Marc, Hendlisz Alain, Sclafani Francesco
Service d'Oncologie Digestive, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium.
Service de Gastroentérologie et Cancérologie Digestive, Hôpital Saint Louis, Paris, France.
Clin Colorectal Cancer. 2025 Mar;24(1):101-105. doi: 10.1016/j.clcc.2024.08.004. Epub 2024 Sep 3.
Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.
COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).
有证据表明，循环肿瘤DNA（ctDNA）可能是监测转移性结直肠癌（CRC）进展的可靠生物标志物。然而，在这种情况下，液体活检潜力的证据质量仍然很低，主要是回顾性研究。
哥白尼研究是一项国际多中心临床试验。该试点研究旨在确认治疗早期ctDNA动态变化的预测潜力，并为一项更大规模的由ctDNA驱动的试验设计提供信息。适合接受≥三线全身治疗的晚期CRC患者在治疗期间（2周或4周治疗方案的第1天、15天和29天；3周治疗方案的第1天、22天和43天）以及每次影像学评估时进行纵向血样采集。使用FoundationOne Liquid CDx和FoundationOneMonitor检测进行ctDNA分析，治疗期间ctDNA的变化与放射学反应相关（根据实体瘤疗效评价标准第1.1版每8 - 12周评估一次）。主要目标是选择早期ctDNA变化（第15/22天）的最佳时间点和临界值，以预测疾病进展，作为具有高阳性预测值的最佳放射学反应。ctDNA的临界值将基于带有自抽样法的非参数ROC曲线来定义。根据预期的疾病进展率和统计假设，需要筛选10例患者才能有87例可评估患者。哥白尼研究由朱尔斯·博尔德研究所赞助，并得到罗氏公司和Foundation Medicine公司的支持。比利时和法国的13个中心正在招募患者。该研究已在clinicaltrials.gov注册（NCT05487248）。
