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Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage III Colon Cancer: A Multicentre Phase II/III Randomised Controlled Study
Other Non-Commercial Sponsor
Walter and Eliza Hall Institute
This is a prospective multi-centre, phase II/III randomised controlled study enrolling a total of 1000 stage III colon cancer patients. Patients will be randomised 1:1 to be treated according to post-op ctDNA results (Arm B: ctDNA-informed), or per standard of care (Arm A: SOC). Enrolment will be stratified by participating centre and clinical risk groups (low risk = T1-3N1; high risk = T4 and/or N2).
Patients should be screened within 21 days after surgery and tumour samples will be made available in 3 working days from consent for mutation analysis. All patients will have a blood draw during week 5-6 post-op for ctDNA analysis (ctDNA-1: post-op day 32 to day 42). Clinicians are to nominate their standard of care adjuvant chemotherapy regimen (no chemotherapy, single agent fluoropyrimidine or combination fluropyrimidine plus oxaliplatin) at the time of enrolment prior to randomisation. Randomisation will occur after the post-op ctDNA blood draw. Additional blood collection time-points will depend on the schedule of adjuvant chemotherapy. Formalin-fixed paraffin embedded tumour tissue and the study bloods sample will undergo ctDNA analysis at Johns Hopkins University.
In the ctDNA-informed arm (Arm B), the post-op ctDNA result will be made available to the treating clinician within 8 weeks post-op. Adjuvant chemotherapy will commence after the ctDNA result becomes available or, where the treating clinician wishes to commence adjuvant treatment before the result is available, an individual patient may commence on standard of care treatment no earlier than 6 weeks post-op, and then switch to the ctDNA informed strategy as per the protocol. Patients who are "ctDNA negative" will be managed with a de-escalation adjuvant treatment strategy and those who are "ctDNA-positive" will be managed with an escalation adjuvant treatment strategy. In the standard of care arm, patients and their clinicians will be blinded to the ctDNA results and will receive adjuvant chemotherapy as per standard of care.
Patients in Arm B receiving 3 or 6 months of adjuvant chemotherapy will have blood collection for ctDNA analysis during treatment (ctDNA-2A +/- ctDNA-2B) and at the end of treatment (ctDNA-3). These results will not be routinely made available to the patients or clinicians.
For patients where standard treatment of oxaliplatin based treatment is escalated to FOLFOXIRI, this will be given for at least 6 cycles.