When cancer cells die, they shed genetic material into the blood stream. This is called circulating tumor DNA (ctDNA) and can be identified with a blood test called Signatera. CtDNA tests are either positive or negative.
This tool has been studied to show it is effective at detecting cancer recurrence. The CIRCULATE-US clinical trial will determine which chemotherapy approach is most effective at treating stage II and III colon cancers after surgery, depending on the results of a ctDNA test.
It is standard of care for stage II or III patients after surgery to receive FOLFOX or CAPOX chemotherapy regimens. “Standard of care” means that this is the regimen you would receive if not in the study. FOLFOX is a combination of the drugs 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. CAPOX is a combination of the drugs capecitabine and oxaliplatin. For many patients, these chemo regimens are equally effective, and are considered equivalent in this trial.
For participants who are ctDNA negative — meaning that Signatera testing found no traces of tumor DNA in their blood — this trial will determine whether or not chemotherapy is necessary after surgery. Patients will be randomized into two groups: One will receive standard FOLFOX for 3 to 6 months or CAPOX for 3 months (Group 1), and the other group will receive no chemotherapy, only regular ctDNA monitoring every 3 months and CT scans every 3 to 6 months (Group 2).
For participants who are ctDNA positive after surgery, this study determines whether standard FOLFOX/CAPOX or FOLFOXIRI is more effective at preventing colon cancer from returning. FOLFOXIRI is a combination of the drugs 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan. FOLFOXIRI is a more aggressive regimen commonly used to treat metastatic (stage IV) CRC. Patients who are ctDNA positive after surgery will be randomized into two groups: One will receive standard FOLFOX/CAPOX for 6 months (Group 3), the other group will receive FOLFOXIRI for 6 months (Group 4).
Patients in Group 2 who eventually test ctDNA positive will be randomized into Group 3 or Group 4.
How does the CIRCULATE-US trial determine treatment efficacy? This trial will measure the time from randomization to the first ctDNA positive test, or recurrence without a ctDNA result. They will also measure the duration of disease-free survival, overall survival, post-surgery ctDNA positivity rate, recurrence rate, and compliance with chemotherapy.
Chemotherapy may cause side effects. There are also potential risks associated with ctDNA testing. Your doctor will review all of the possible risks with you.