FOxTROT 3
Status: Open
Title
FOxTROT 3: A phase III randomized trial evaluating neoadjuvant chemotherapy with mFOLFOXIRI compared with neoadjuvant OxFp in patients with locally advanced but operable colon cancer.
Description
FOxTROT 1 reported that neoadjuvant chemotherapy (NAC) with OxFp (oxaliplatin-fluoropyrimidine) was safe and resulted in improved shortand long-term cancer outcomes compared with straight to surgery (STS) for patients with operable colon cancer. It also demonstrated close correlation between histological tumour regression grade after NAC (TRG) and long-term outcomes. However, in around one-third of patients no histological tumour regression was evident after 6 weeks of NAC with OxFp.
In metastatic colorectal cancer (mCRC), modified oxaliplatinfluoropyrimidine-irinotecan (mFOLFOXIRI) plus bevacizumab is associated with improved response rates (RR), progression-free survival (PFS), and overall survival (OS) compared with FOLFIRIbevacizumab. In FOxTROT 3 we will evaluate intensification of the 6-week period of NAC with mFOLFOXIRI compared with OxFp in patients with locally advanced but resectable colon cancer of good performance status (PS).
We hypothesise that mFOLFOXIRI will increase the proportion of patients with high-grade responses, and reduce the proportion with no response to NAC, compared with OxFp, and that this will improve longer term outcomes.
Objectives
To assess and compare whether 6 weeks of NAC with mFOLFOXIRI followed by surgery will improve the proportion of patients with a pathological response to NAC (as assessed in the surgical resection sample) according to tumour regression grade (TRG), disease-free survival (DFS) and short-term safety and efficacy outcomes compared with 6 weeks of NAC with OxFp followed by surgery.
Trial Design
Randomised, phase III, multi-centre, international, open-label study.
Trial Status
Open
Population
Participants will have locally advanced but operable colon cancer (CC). Patients need to be fit and suitable for mFOLFOXIRI and they will therefore be medically fit with normal renal, hepatic and cardiac function. There is no fixed age cut-off, but we anticipate most patients will be under 70 years.
Patients with right sided tumours (proximal to the splenic flexure) will be included only if MMR proficient (pMMR)/ microsatellite stable (MSS) status is confirmed. All patients with left-sided tumours can be randomised without mandatory MMR/ microsatellite instability (MSI)