Rechallenge of Cetuximab Combined With Irinotecan as Third-line Chemotherapy in Patients With Metastatic Colorectal Cancer - Phase II Study

Inclusion Criteria:

* Signed and dated informed consent
* Histologically confirmed metastatic adenocarcinoma of the colon or rectum
* All Wild Type KRAS (exon 2 \[codons 12-13\], exon 3 \[codons - 61\]; exon 4 \[codon 146\]), NRAS (exon 2 \[ codons 12-13\] and exon 3 \[codon 61) and BRAF (V600E) tumor ( local assessment performed either on primary tumor or metastasis)
* First line chemotherapy regimen with a fluoropyrimidine and Irinotecan (FOLFIRI) + cetuximab with initial partial or complete response and progressive disease (PD) with PD ≤ 6 weeks after the last administration of cetuximab
* Other line(s) of therapy(ies) including the following drugs: second line oxaliplatin based chemotherapy with fluoropyrimidines (5FU or capecitabine) + bevacizumab and eventually regorafenib (possible but not mandatory) and progression or limiting toxicity to the last therapy with a minimum of 4 months between last injection of cetuximab and inclusion in this study
* At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 (All sites must be evaluated ≤ 28 days prior to the enrolment)
* Age ≥18 years
* World Health Organization (WHO) Performance status (PS) 0-2
* The patient has adequate organ function, defined as :

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 100 x 109/L.Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level \< 5 times ULN, Serum creatinine level \<150μM/l

* For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug
* Men and women are required to use adequate birth control during the study (when applicable) and until 6 months after the end of study treatment
* Registration in a national health care system (CMU included)

Exclusion Criteria:

* Previous chemotherapy other than adjuvant therapy with different combinations than those scheduled in first and second line treatment
* Presence of any KRAS, BRAF or NRAS mutation by allelic discrimination on tumor DNA
* Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not)
* History or evidence of central nervous system metastasis (systematic CT-scan or MRI not mandatory if no clinical symptoms)
* Known allergy or hypersensitivity to cetuximab
* Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study
* Active or uncontrolled clinically serious infection
* Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
* Other serious and uncontrolled non-malignant disease
* Pregnancy
* Breast feeding
* Treatment with any other investigational medicinal product within 28 days prior to study entry
* Known Gilbert's syndrome
* Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine
* Concomitant use with St John's Wort
* Chronic inflammatory bowel disease and/or Bowel obstruction