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 ( localassessment 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) withPD ≤ 6 weeks after the last administration of cetuximab

• Other line(s) of therapy(ies) including the following drugs: second line oxaliplatinbased chemotherapy with fluoropyrimidines (5FU or capecitabine) + bevacizumab andeventually regorafenib (possible but not mandatory) and progression or limitingtoxicity to the last therapy with a minimum of 4 months between last injection ofcetuximab and inclusion in this study

• At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI (MagneticResonance Imaging) according to RECIST v1.1 (All sites must be evaluated ≤ 28 daysprior 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 alkalinephosphatase level < 5 times ULN, Serum creatinine level <150μM/l

• For female patients of childbearing potential, negative pregnancy test within 7 daysbefore starting the study drug

• Men and women are required to use adequate birth control during the study (whenapplicable) 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 thanthose 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 infarctionwithin 12 months before initiation of study treatment or a history of ventriculararrhythmia (treated or not)

• History or evidence of central nervous system metastasis (systematic CT-scan or MRInot mandatory if no clinical symptoms)

• Known allergy or hypersensitivity to cetuximab

• Previous or concurrent malignancy except for basal or squamous cell skin cancer, insitu carcinoma of the cervix, low-risk prostate cancer according to d'Amicoclassification or other solid tumors treated curatively and without evidence ofrecurrence for at least 5 years prior to the study

• Active or uncontrolled clinically serious infection

• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiencysyndrome (AIDS)-related illness

• Other serious and uncontrolled non-malignant disease

• Pregnancy

• Breast feeding

• Treatment with any other investigational medicinal product within 28 days prior tostudy entry

• Known Gilbert's syndrome

• Concomitant administration of live, attenuated virus vaccine such as yellow fevervaccine

• Concomitant use with St John's Wort

• Chronic inflammatory bowel disease and/or Bowel obstruction