Safety and Efficacy Study of FOLFOX4+Panitumumab vs.FOLFIRI+Panitumumab in Subjects WT KRAS Colorectal Cancer and Liver-only Metastases

Inclusion Criteria:

* Man or woman \> 18 years \< 75 of age
* Competent to comprehend, sign, and date an IEC-approved informed consent form
* Histologically confirmed adenocarcinoma of the colon or rectum
* Wild Type KRAS status
* Metastatic colorectal carcinoma exclusively affecting only the liver, compliant with one of the following criteria

  1. Number of liver metastasis ≥ 4.
  2. Size of one liver metastasis \> 10 cm in diameter.
  3. Liver metastases technically not resectable.
* At least 1 uni-dimensionally measurable lesion
* Patients with the following characteristics will be included:

  1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval \> than 6 months after its completion; or after oxaliplatin containing adjuvant treatment with a disease-free interval \> than 12 months
  2. Recurrence after surgical treatment and/or radiotherapy with no adjuvant systemic treatment.
  3. De novo diagnosis of the disease.
* Patients with simultaneous liver metastases are eligible, if the primary tumor has been resected at least 1 month prior chemotherapy.
* Prior radiotherapy is acceptable.
* Patients deemed to have no major contra-indication to liver surgery from a general health perspective.
* Karnofsky performance status ≥ 70%
* Adequate bone marrow function: neutrophils ≥ 1.5 x109/ L; platelets ≥ 100 x109/ L;hemoglobin ≥ 9g/ dL
* Hepatic and metabolic function as follows:

Total bilirubin count ≤ 1.5 x ULN and not increasing more than 25% within the last 4 weeks; ALAT and ASAT \< 5 x ULN;

* Renal function, calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.
* Magnesium \> LLN

Exclusion Criteria:

* Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, erlotinib).Subjects who have experienced an infusion reaction to their first dose of anti-EGFR therapy (cetuximab) may participate in this clinical trial.
* Surgery (not including diagnostic biopsy) and/or radiotherapy in the 4 weeks prior to inclusion in the study.
* Metastasis on any site other than the liver, including extrahepatic lymph nodes.
* Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive carcinoma of the skin.
* Systemic chemotherapy, hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, bevacizumab) ≤ 30 days before inclusion
* Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for inclusion
* Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan
* Treatment for systemic infection within 14 days before initiating study treatment
* Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as \> 4 loose stools per day)
* History of Gilbert's syndrome or dihydropyrimidine deficiency
* History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results
* Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
* subject allergic to the ingredients of the study medication or to Staphylococcus protein A
* Any co-morbid disease that would increase risk of toxicity
* Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
* Any investigational agent within 30 days before enrolment
* Must not have had a major surgical procedure within 28 days of randomization
* Subject who is pregnant or breast feeding
* Woman or man of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men
* Subject unwilling or unable to comply with study requirements