First-line treatment with FOLFIRI chemotherapy and cetuximab, with or without a break, for metastatic colorectal cancer with wild-type RAS/BRAF

Metastatic colorectal cancer is an advanced form of colorectal cancer in which the tumor has already spread to other organs (metastases) and can no longer be surgically removed. Cetuximab is a monoclonal antibody that specifically binds to the epidermal growth factor receptor (EGFR) on the tumor surface, thereby blocking signals that promote the growth and division of cancer cells. The FOLFIRI chemotherapy regimen consists of the active ingredients 5-fluorouracil, folinic acid, and irinotecan and is administered intravenously. Cetuximab can only be effective if the tumor has no mutations in either the RAS gene or the BRAF gene (known as RAS/BRAF wild-type).

The goal of this Phase 3 study is to investigate whether treatment with FOLFIRI and cetuximab, with scheduled treatment breaks, is just as effective as continuous treatment and whether this approach can improve quality of life and reduce side effects. Patients will be randomly assigned to two parallel groups. In the control arm, FOLFIRI combined with cetuximab is administered continuously as long as the disease does not worsen. In the study arm, the same therapy is paused as scheduled after up to six treatment cycles and resumed only when there are signs of renewed disease activity. The study is open-label (not blinded), meaning that both the study physicians and the patients know which treatment is being administered. To guide the treatment interruption strategy, accompanying questionnaires and blood tests for circulating tumor DNA (ctDNA) are used, which can detect signs of renewed tumor growth in the blood.

Eligible participants are patients aged 18 years or older with histologically confirmed, inoperable adenocarcinoma of the colon or rectum at UICC stage IV, whose tumor has been centrally confirmed as RAS/BRAF wild-type. Patients must not have received prior chemotherapy for metastatic colorectal cancer. Chemotherapy completed following a previous surgery (adjuvant chemotherapy) that took place more than six months ago is permitted. Patients with a confirmed RAS or BRAF mutation, a history of brain metastases, or severe comorbidities are not eligible to participate.