The CIRCULATE Trial: Circulating Tumor DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (AIO-KRK-0217).
Adjuvant treatment
Chemotherapy
Colon cance
Randomised trial
ctDNA
Journal
Clinical colorectal cancer
ISSN: 1938-0674
Titre abrégé: Clin Colorectal Cancer
Pays: United States
ID NLM: 101120693
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
10
05
2021
accepted:
09
09
2021
pubmed:
14
11
2021
medline:
31
5
2022
entrez:
13
11
2021
Statut:
ppublish
Résumé
Guidance regarding adjuvant treatment decisions in stage II colorectal cancer (CRC) remains uncertain due to lack of predictive clinical or molecular markers. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be a strong prognostic marker in early colon cancer. CIRCULATE enrols patients with stage II microsatellite stable CRC in Germany (AIO) and Austria (ABCSG). Within the AIO, screening is supported by ColoPredict Plus 2.0, a molecular registry, and screening platform for interventional trials. Patient-specific mutations are centrally analysed by next generation sequencing in the resected primary tumour. A postoperative plasma sample is subsequently screened for the specific mutation(s). ctDNA positive (ctDNApos) patients are randomised (2:1) chemotherapy (capecitabine, oxaliplatin added an investigator's choice) or to follow-up (control group). ctDNA negative (ctDNAneg) patients are randomised (1:4) to be followed-up within CIRCULATE (control group) or outside the trial. Patients in the control group remain blinded to the ctDNA results. The primary objective is to compare disease free survival (DFS) of ctDNApos patients with chemotherapy or control. To demonstrate a treatment effect with a hazard ratio of 0.617 (3-year DFS rates 42.5% vs. 25%), 231 ctDNApos and estimated 2079 ctDNAneg patients are randomised. Secondary aims include to compare overall survival and DFS in the ctDNApos and ctDNAneg patient cohorts and ctDNA kinetics. The CIRCULATE trial may establish ctDNA for adjuvant treatment decision in stage II colon cancer - and with the secondary objectives - support a ctDNA guided follow up in colon cancer stage II and beyond.
Sections du résumé
BACKGROUND
Guidance regarding adjuvant treatment decisions in stage II colorectal cancer (CRC) remains uncertain due to lack of predictive clinical or molecular markers. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be a strong prognostic marker in early colon cancer.
PATIENTS AND METHODS
CIRCULATE enrols patients with stage II microsatellite stable CRC in Germany (AIO) and Austria (ABCSG). Within the AIO, screening is supported by ColoPredict Plus 2.0, a molecular registry, and screening platform for interventional trials. Patient-specific mutations are centrally analysed by next generation sequencing in the resected primary tumour. A postoperative plasma sample is subsequently screened for the specific mutation(s). ctDNA positive (ctDNApos) patients are randomised (2:1) chemotherapy (capecitabine, oxaliplatin added an investigator's choice) or to follow-up (control group). ctDNA negative (ctDNAneg) patients are randomised (1:4) to be followed-up within CIRCULATE (control group) or outside the trial. Patients in the control group remain blinded to the ctDNA results. The primary objective is to compare disease free survival (DFS) of ctDNApos patients with chemotherapy or control. To demonstrate a treatment effect with a hazard ratio of 0.617 (3-year DFS rates 42.5% vs. 25%), 231 ctDNApos and estimated 2079 ctDNAneg patients are randomised. Secondary aims include to compare overall survival and DFS in the ctDNApos and ctDNAneg patient cohorts and ctDNA kinetics.
CONCLUSION
The CIRCULATE trial may establish ctDNA for adjuvant treatment decision in stage II colon cancer - and with the secondary objectives - support a ctDNA guided follow up in colon cancer stage II and beyond.
Identifiants
pubmed: 34772609
pii: S1533-0028(21)00091-8
doi: 10.1016/j.clcc.2021.09.005
pii:
doi:
Substances chimiques
Circulating Tumor DNA
0
Oxaliplatin
04ZR38536J
Capecitabine
6804DJ8Z9U
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-174Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest GF received honoraries for lectures from Amgen, Bayer, BMS, Falk Foundation, Merck, MSD, Roche, Servier, Shire, honoraries for advisory boards from Amgen, Bayer, BMS, Merck, MSD, Pierre Fabre, Roche, Sanofi-Aventis, Servier, Shire and research funding from Merck. ARS received honoraries for lectures fromAmgen, AstraZeneca, Aurikamed, BMS, Celgene, iomedico, Lilly, Merck Serono, MCI Global, med publico, MSD, Pfizer, promedicis, Roche, Sanofi-Aventis, Servier , honoraries for advisory boards from Amgen, AstraZeneca, Baxalta, BMS, Celgene, Merck Serono, MSD, Onkowissen.de, Pierre Fabre, Pfizer, Roche, Servier, Onkowissen.de , travel expenses from AstraZeneca, Celgene, Ipsen, MCI Global, Merck Serono, MSD, onkowissen.de, Pierre Fabre, Roche, Servier and research funding for clinical studies from Roche and Ipsen, and compensation for clinical trials / research from Amgen, Alexion, Astra Zeneca, Celgene, Ipsen, Lilly, Roche, Servier, AIO Studien gGmbH, Agricola, PPD Global Limited UK, Mologen Berlin, Universität München, Universität Erlangen, Universität Köln, Pharma Consulting Group AB Schweden, Syneed medidata GmbH, Rafael-Pharmaceutics; BioNTech. LW has stocks from Guardant Health, received honoraries for lectures from Roche;Bristol-Myers Squibb; Lilly; Novocure; Merck Serono; Amgen; Pierre Fabre; Servier; MSD, honoraries for advisory boards from Bristol-Myers Squibb; Roche; Lilly; Novocure; Merck Serono; Takeda; MSD; Amgen; PharmaMar; Bayer, received research funding from Roche and Novocure and travel expenses from Ipsen; Pfizer; Merck Serono; Astra Zeneca. NvB received honoraries for lectures from Forum für Medizinische Fortbildung (FomF)CT has partly ownership at AgenDix GmbH and received honoraries for advisory boards from JAZZ, Novartis, honoraries for lectures from Novartis, Astellas, JAZZ, Janssen; Thermo and research funding from Novartis, Bayer and JAZZ. AT received honoraris for lecture from Amgen, AstraZeneca, BMS, Celgene, iomedico, Lilly, Merck Serono, MCI Global, med publico, MSD, Pfizer, promedicis, Roche, Sanofi-Aventis, Servier and support for clinical studies / research from Amgen, Alexion, Astra Zeneca, Celgene, Ipsen, Lilly, Roche, Servier, AIO Studien gGmbH, BioNTech. JW, CL, ALK,SW,DEA, and MK declared no conflicts of interest.