Cetuximab Rechallenge in Irinotecan-pretreated mCRC, KRAS, NRAS and BRAF Wild-type Treated in 1st Line With Anti-EGFR Therapy (CRICKET).

Inclusion Criteria:

* Histologically proven diagnosis of colorectal adenocarcinoma;
* RAS and BRAF wild-type status;
* First-line irinotecan-based (FOLFIRI or FOLFOXIRI) cetuximab-containing therapy producing at least a partial response;
* First-line progression-free survival in response to cetuximab-containing therapy ≥6 months;
* Documentation of progression to first-line cetuximab within 4 weeks after last cetuximab administration;
* Time between the end of first-line therapy and the start of third-line treatment with cetuximab plus irinotecan ≥4 months;
* Second-line oxaliplatin-based (FOLFOXIRI, FOLFOX or XELOX) bevacizumab-containing therapy;
* Documentation of progression to second-line treatment;
* Measurable disease according to RECIST criteria v1.1;
* Have tumor tissue (of primary tumor and metastases or at least one of the two) available for biomarker analysis;
* Male or female patients \> 18 years of age;
* ECOG Performance Status ≤ 2;
* Life expectancy of at least 3 months;
* Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment;
* Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile or are sexually inactive;
* Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicidal or intrauterine device. This requirement begins 2 weeks before receiving the first trial treatment and ends 6 months after receiving the last treatment;
* Signed informed consent obtained before any study specific procedure.

Exclusion Criteria:

* Active uncontrolled infections or active disseminated intravascular coagulation;
* Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
* Fertile women (\< 12 months after last menstruation) and men of childbearing potential not willing to use effective means of contraception
* Women who are pregnant or are breastfeeding;
* Previous grade 3/4 infusion related reaction to cetuximab.