FOxTROT 5
Status: In set-up
Title
FOxTROT 5: A phase II single-arm trial evaluating perioperative dostarlimab in older and/or frail patients with locally advanced but operable deficient mismatch repair colon cancer.
Description
Tumour microsatellite instability (MSI) and mismatch repair enzyme deficiency (dMMR) are associated with a favourable prognosis in locally advanced colon cancer (CC), but lesser benefit from adjuvant and neoadjuvant chemotherapy.
Initial results from phase II trials of neoadjuvant immunotherapy (NAI) in locally advanced dMMR/MSI-high (MSI-H) colon and rectal cancer have been remarkable. However, while over 40% of all new cases of colorectal cancer (CRC) are diagnosed in people aged 75 years and over, the median age of participants in these trials was considerably less, and all but two patients had ECOG performance status 0 or 1 – meaning efficacy in older and more frail patient groups has not yet been demonstrated.
We hypothesise that in older and/or frail patients with untreated locally advanced dMMR/MSI-H CC, 12 weeks of neoadjuvant dostarlimab (an anti-PD1 monoclonal antibody) prior to surgery with curative intent, followed by 36 weeks of post-operative dostarlimab, will demonstrate similar efficacy to that seen in younger and fitter populations.
Within a response evaluation exploratory substudy, CT colonography and colonoscopy at the end of the neoadjuvant treatment period will be performed in a subset of participants, in order to assess the utility of these investigations for evaluating response to treatment.
Objectives
To assess the efficacy and safety of 12 weeks of neoadjuvant dostarlimab prior to surgery with curative intent, followed by 36 weeks of postoperative dostarlimab.
The trial will incorporate a response evaluation exploratory substudy in a subset of participants in whom we will evaluate treatment response assessments (CT colonography, and colonoscopy with biopsy). These will be compared to pathology at time of resection in order to investigate a potential relationship between the response assessments and pathology.
Trial Design
Single-arm, two-stage, phase II, multi-centre, open-label study.
Trial Status
In setup
Population
Patients with locally advanced but operable dMMR/MSI-H CC aged 70 years or more and/or with investigator-assessed frailty.