Randomized study to compare first-line treatment with either continuous or intermittent cetuximab plus FOLFIRI in patients with RAS/BRAF-wild-type metastatic colorectal cancer (mCRC): AIO-KRK-0524 / FIRE-11

Condition studied

metastatic colorectal cancer

Investigational medicinal product(s)

Eligibility

Primary endpoint

Time to Failure of Strategy, which is defined as the time from randomization to failure of the treatment strategy. Failure of the treatment strategy is defined as o Disease progression on treatment o Death o Unacceptable toxicity o Occurrence of resistance mechanisms by ctDNA analysis

Endpoint detail

Efficacy: • Progression-free survival (PFS)1 to PFSN (defined as each PFS from treatment start with FOLFIRI+cetuximab to the first disease progression in the respective treatment period) • TFS stratified by ctDNA-guided progression or radiological progression • Overall survival (OS) • Objective response rate (ORR), Tumor response kinetics: • Dynamics of the tumor markers CEA and CA19-9 • Early tumour shrinkage, as determined by radiological imaging • Depth of radiological tumor response, as determined by radiological imaging, Circulating tumour DNA (ctDNA): • Prospective validation to use ctDNA based RAS/BRAF mutational analysis in addition to tissue-based RAS testing to exclude RAS/BRAF mutant tumors from treatment using the Guardant360 liquid biopsy assay • Define a threshold in ctDNA change predicting progressive disease during treatment break using the Guardant360 liquid biopsy assay • Validate the formerly defined ctDNA threshold using the Guardant360 liquid biopsy assay to induce re-use of FOLFIRI + Cetuximab, Safety: • Type, incidence, severity, and causal relationship to IMPs of non-serious adverse events and serious adverse events (severity evaluated according to CTCAE version 5.0), Quality of life: • QoL as assessed with the QoL questionnaire EQ-5D-5L