Study Evaluating Biomarkers in Patients With Colorectal Cancer and Native KRAS Treated With Chemotherapy + Cetuximab

Inclusion Criteria:

* Male or female, age ≥ 18 years
* Able to sign an informed consent form
* Advanced and/or metastatic colorectal cancer
* Colorectal cancer with KRAS wild type genotype
* At least one unidimensionally measurable lesion according to RECIST criteria (1.1 revised) (to be assessed ≤ 28 days prior to the study treatment)
* All patients with the following features will be included:

  1. Progression free survival \> 6 months after adjuvant treatment +/- radiotherapy
  2. "De novo" diagnosis of the disease
* Performance ECOG status of 0-2
* Life expectancy ≥ 3 months
* Adequate bone marrow function: neutrophils ≥1,5 x 10\^9/L; platelets ≥ 100 x 10\^9/L; hemoglobin ≥9 g/dL.
* Adequate liver, renal and hematological function as follows:

  1. Adequate liver function: SGOT and SGPT 2.5 x ULN (5 x ULN in case of hepatic metastasis). Total bilirubin \< 1,5 x ULN. Alkaline phosphatase 2,5 x LSN (5 x ULN if hepatic metastasis or 10 x ULN if bone metastasis)
  2. Creatinine clearance or creatinine clearance during 24 hours ≥ 50 mL/min
  3. Magnesium ≥ LLN, calcium ≥ LLN

Exclusion Criteria:

* PS \> 2 or elderly patients with fragility criteria
* Previous surgery for metastasis
* Previous systemic treatment for the metastatic colorectal cancer
* Previous treatment with antibodies anti-EGFR or treatment with small-molecule EGFR tyrosine kinase inhibitors or EGFR signal transduction inhibitors. Subjects who suspend their first dose due to a reaction to the infusion can participate
* Central nervous system metastasis (except: treated subjects with asymptomatic CNS metastasis who have not received steroids within the 30 days prior to inclusion)
* Prior malignant tumor in the last 5 years, except: basal cell carcinoma of the skin or pre-invasive cervical cancer
* Unresolved toxicities from a prior systemic treatment which do not qualify the patient for inclusion
* Presence of peripheral neuropathy (degree \> 1 in the ctc version 3.0) and serious nonhealing wound, ulcer, or bone fracture
* Hormonal treatment, immunotherapy or experimental or approved antibodies/proteins ≤ 30 days before the inclusion
* Uncontrolled serious cardiovascular disease or: congestive cardiac failure NYHA lll or lV, unstable angina pectoris, myocardial infarction precedents in the past 12 months, significant arrhythmias
* Interstitial pneumonitis or pulmonary fibrosis precedents, or interstitial pneumonitis or pulmonary fibrosis signs on the thoracic CT-scan
* Treatment for systemic infection within the 14 days prior to treatment
* Acute/subacute intestinal occlusion and/or active inflammatory bowel disease or any other bowel disease producing chronic diarrhea
* Precedent of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency
* Precedent of any disease which can increase the risks associated to the participation in the study or interfere in the study results
* Known positive test for the following infections: HIV, Hepatitis C + abnormal liver enzymes values, active chronic Hepatitis B (except Hepatitis C seropositive with normal liver enzymes)
* All concurrent diseases which can increase the toxicity risk
* The individual presents a disorder of any kind which jeopardizes their ability to give their written consent form and/or fulfill the study procedures
* Any investigational agent within 30 days before enrolment
* Pregnant or breastfeeding woman, or planning to get pregnant within the 6 months after treatment
* Surgery (excluding the diagnostic biopsy or placing of a central venous catheter)
* Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the study and 6 months after de last administration for women, and 1 month for men
* Unability to fulfill the study requirements by the patients
* Psychological, family, sociological or geographical conditions that may interfere with the fulfillment of the study protocol and the follow-up calendar