Study of FOLFIRI + Panitumumab Using Ultra-selection Technology of Patients With Stage IV Colorectal Cancer Refractory to Irinotecan Without Any Mutation on KRAS, PIK3Ca, BRAF and NRAS Genes Detected With Highly Sensitive Techniques

Inclusion criteria

• Competent to understand, sign and date an IEC-approved informed consent form.
• Men or women 18 years of age or older at the time the written informed consent is obtained.
• Histologically confirmed metastatic adenocarcinoma of the colon or rectum Wild-Type RAS (No mutation) with at least 1 measurable metastatic lesion following RECIST criteria v 1.1 and initially irresectable (non suitable for radical surgery at the inclusion time).
• Obtention of DNA from tumor tissue blocks sent to central lab (ICO) that is amenable for highly sensitive techniques
• Previous irinotecan based chemotherapy +/- bevacizumab for metastatic CCR during at least 6 weeks.
• Irinotecan based chemotherapy does not need to be the most recent chemotherapy administrated. There are no restrictions on numbers of treatments lines before study inclusion.
• Disease progression during irinotecan treatment or within 6 months after irinotecan treatment.
• Karnofsky status ≥ 70% .
• Adequate bone marrow, hepatic, renal and metabolic functions,

• Adequate bone marrow function: neutrophils ≥ 1.5x109/ L; platelets ≥ 100x109/L; hemoglobin ≥ 9g/dL.
• Hepatic functions as follows: total bilirubin count ≤ 1.5 x ULN; ALAT and ASAT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis).
• Renal function: creatinine clearance > 50 ml/min (according Cockcroft y Gault formulae)
• Metabolic functions: magnesium ≥ lower limit of normal (LIN)
• Life expectancy ≥ 3 months.

Exclusion criteria

• Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer.
• Unresolved toxicities from prior systemic therapy and/or radiotherapy that, in the opinion of the investigator, does not qualify the patient for inclusion.
• Documented or suspected central nervous system metastases.
• Any previous antitumoral treatment (chemotherapy, hormonal therapy, radiation treatment, surgery, immunotherapy, biologic therapy) ≤ 28 days before study inclusion.
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
• Prior anti-EGFr antibody therapy (eg, Cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, Erlotinib). Subjects who discontinue their first dose of anti-EGFR therapy (Cetuximab) because of an infusion reaction may participate in this clinical trial.
• Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor not available or quality ADN not available for biomarker determination by highly sensitive techniques.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
• Treatment for systemic infection within 14 days before study inclusion.
• Acute or sub-acute intestinal occlusion and /or 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, and 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.
• Subject who is pregnant or breast feeding.
• Surgery (excluding diagnostic biopsy or central venous catheter placement) ≤ 28 days prior study inclusion.
• Woman or man of childbearing potential not consenting to use adequate contraceptive precautions.
• Subject unwilling or unable to comply with study requirements.
• Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.