In this exploratory phase II trial, the possibility of a personalized treatment after resistance to cetuximab will be evaluated. Therefore, tumor material of all patients shall be obtained, transferred into avatars and treated the same way as in the patient until resistance arises. These resistant tumor cells are subsequently treated by different targeted treatment combinations in the mouse avatar model to find the most active drug or combination of drugs. This drug or combination of drugs may then be offered to the patient after cetuximab resistance has occurred. Multiple liquid biopsies shall be obtained in patients during first‐line treatment with cetuximab as well as during second line experimental treatment to monitor mutations that may be associated with cetuximab resistance. Furthermore at the time of resistance a biopsy should be taken and analyzed to ensure that the mechanism of resistance seen in the avatar model matches with the mechanism of resistance in the individual patient.