Nordic 8 - A Phase II Trial

Inclusion criteria

Histology and stages:

• Histologically proven adenocarcinoma in the colon or rectum
• At least 1 measurable metastatic disease manifestation according to the RECIST criteria (version 1.1)
• Potentially completely resectable or potentially curable metastatic colorectal cancer as determined by the local MDT conference and that requires tumour shrinkage before resection is possible. The following definitions are indicative:

• 4 or more liver metastases (CRLeM) without extra-hepatic disease
• 2 or more lung metastases (CRLuM) without hepatic or extra-hepatic disease
• 1 or more CRLeM determined as "potentially resectable" (such as because of location) by the local MDT.
• 1 or more CRLuM determined by the local MDT as potentially resectable (such as because of location).
• Non-resectable primary disease with resectable CRLeM or CRLuM.

KRAS and BRAF status:

• Tumour tissue (primary or metastasis) typed as wild-type KRAS AND wild-type BRAF

General conditions:

• age > 18 years
• WHO performance status ≤ 1
• expected survival > 3 months
• sufficient bone-marrow function (Hb ≥ 6.2 µmol/l/Hb > 10 g/dl ANC ≥ 1.5 x 109/l, thrombocytes ≥ 100 x 109/l)
• sufficient kidney and liver function: total bilirubin ≤ 1.5 x upper normal limit, serum creatinine ≤ 1.25 x upper normal limit, ALAT ≤ 3 x upper normal limit and ≤ 5 x upper normal limit with liver metastases
• the patient must have signed an informed declaration of consent before being registered; this must be documentable according to national guidelines

Exclusion criteria

Previous treatment:

• previous chemotherapy for advanced/metastatic disease
• adjuvant chemotherapy unless completed more than 6 months before registration
• previous treatment with oxaliplatin or irinotecan
• previous treatment with cetuximab or other treatment for EGFR
• History of Inflammatory Bowel disease
• Severe or uncontrolled cardiovascular disease, congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
• Any condition that, according to the treating physician's judgement, could prevent the planned medical/surgical treatment from being carried out responsibly (such as uncontrolled active infection, known hypersensitivity or contra-indication for the planned treatment.
• Pregnant or breast-feeding women
• Patients of fertile age who do not want to use reliable contraception