Open Label Phase II Study of FOLFIRI + Panitumumab Using Ultra-selection Technology With Next Generation High Sensitivity Genotyping 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.
1. Competent to understand, sign and date an IEC-approved informed consent form.
2. Men or women 18 years of age or older at the time the written informed consent is
3. Histologically confirmed metastatic adenocarcinoma of the colon or rectum Wild-Type
KRAS (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
4. Obtention of DNA from tumor tissue blocks sent to central lab (ICO) that is amenable
for highly sensitive techniques
5. Previous irinotecan based chemotherapy +/- bevacizumab for metastatic CCR during at
least 6 weeks.
6. Irinotecan based chemotherapy does not need to be the most recent chemotherapy
administrated. There are no restrictions on numbers of treatments lines before study
7. Disease progression during irinotecan treatment or within 6 months after irinotecan
8. Karnofsky status ≥ 70% .
9. Adequate bone marrow, hepatic, renal and metabolic functions,
1. Adequate bone marrow function: neutrophils ≥ 1.5x109/ L; platelets ≥
100x109/L; hemoglobin ≥ 9g/dL.
2. 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).
3. Renal function: creatinine clearance > 50 ml/min (according Cockcroft y Gault
4. Metabolic functions: magnesium ≥ lower limit of normal (LIN)
10. Life expectancy ≥ 3 months.
1. Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma
of the skin or pre-invasive cervical cancer.
2. Unresolved toxicities from prior systemic therapy and/or radiotherapy that, in the
opinion of the investigator, does not qualify the patient for inclusion.
3. Documented or suspected central nervous system metastases.
4. Any previous antitumoral treatment (chemotherapy, hormonal therapy, radiation
treatment, surgery, immunotherapy, biologic therapy) ≤ 28 days before study
5. Significant cardiovascular disease including unstable angina or myocardial infarction
within 12 months before initiating study treatment or a history of ventricular
6. 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.
7. Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor
not available or quality ADN not available for biomarker determination by highly
8. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial
pneumonitis or pulmonary fibrosis.
9. Treatment for systemic infection within 14 days before study inclusion.
10. 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).
11. History of Gilbert's syndrome or dihydropyrimidine deficiency.
12. History of any medical condition that may increase the risks associated with study
participation or may interfere with the interpretation of the study results.
13. Known positive test for human immunodeficiency virus infection, hepatitis C virus,
and chronic active hepatitis B infection.
14. Subject allergic to the ingredients of the study medication or to Staphylococcus
15. Any co-morbid disease that would increase risk of toxicity.
16. Any kind of disorder that compromises the ability of the subject to give written
informed consent and/or comply with the study procedures.
17. Subject who is pregnant or breast feeding.
18. Surgery (excluding diagnostic biopsy or central venous catheter placement) ≤ 28 days
prior study inclusion.
19. Woman or man of childbearing potential not consenting to use adequate contraceptive
20. Subject unwilling or unable to comply with study requirements.
21. Psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule.