The CIRCULATE study evaluates the adjuvant therapy in patients with colon cancer UICC stage II. The primary aim of the study is to compare the disease free survival in patients who are positive for postoperative circulating tumour DNA with vs. without capecitabine.
Resected colon cancer stage II, OR Resected rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum ), so that the treatment follows the recommendations for colon cancer. Patients, in whom the tumour stage is not yet know, can be enrolled into the screening.
Signed informed consent for the screening Phase
Resected colon cancer stage II, OR resected rectal cancer stage II, if there was no indication for radiotherapy (i.e. due to the localisation in the upper third of the rectum), so that the treatment follows the recommendations for colon cancer.
Known microsatellite or mismatch repair status
Patients with known microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR)
Known clinical high risk situation if it is regarded as certain indication for an adjuvant chemotherapy
Patients, who have an obvious contra-indication for adjuvant chemotherapy (i.e. due to the performance status, comorbidity, active second cancer or age). It should be considered that patients with an age of more than 75 years frequently not fulfil criteria for adjuvant chemotherapy.
R1- or R2-status (patients with [still] unknown R-status can be screened)
Parallel
Capecitabine
Drug6 months capecitabine, in combination with oxaliplatin 3 to 6 months capecitabine
Disease free Survival (DFS)
Disease free survival of ctDNA positive patients randomised to "chemotherapy" vs. "follow-up", measured from randomisation to any recurrence, metastasis, second colorectal or non colorectal cancer and death from any cause. The primary endpoint will be tested in all randomised ctDNA positive patients and be evaluated by a stratified log rank test. Interims analysis after 93 events (approx. 38 months after study start), final analysis for the primary endpoint after 154 events (approx. 60 months after study start).
Overall survival in ctDNApos patients with adjuvant therapy vs follow-up
Overall survival in ctDNApos patients with adjuvant therapy vs follow-up, measured from randomisation to death from any cause, in all randomised ctDNA positive patients and be evaluated by a stratified log rank test.
Disease free survival in ctDNAneg patients randomised to follow up
Disease free survival in ctDNAneg patients randomised to follow up (rate of patients disease free and alive 3 years after randomisation according to Kaplan-Meier estimation with 95% CI, intention-to-treat analysis). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause is regarded as event (rate of patients disease free and alive 3 years after randomisation according to Kaplan-Meier estimation with 95% CI, intention-to-treat analysis). Any recurrence, metastasis, second colorectal or non- colorectal cancer and death from any cause is regarded as event
Overall survival in ctDNAneg patients randomised to "follow up"
Overall survival in ctDNAneg patients randomised to "follow up" (rate of patients alive after 5 years after randomisation according to Kaplan-Meier estimation with 95% CI)
Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to "follow-up"
Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to "follow-up" (measured from randomisation to the event in an intention-to-treat analysis by stratified log rank test). Any recurrence, metastasis, second colorectal or non-colorectal cancer and death from any cause are regarded as event for DFS. Death of any cause will be regarded as event for overall survival.
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