Abstract
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.
Keywords
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Article info
Publication history
Published online: September 14, 2021
Accepted:
September 9,
2021
Received:
May 10,
2021
Identification
Copyright
© 2021 Published by Elsevier Inc.
