Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of mCRC
* RAS wild-type status (by a Clinical Laboratory Improvement Amendments \[CLIA\] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog \[KRAS\], Harvey rat sarcoma viral oncogene homolog \[HRAS\], and neuroblastoma RAS viral (v-ras) oncogene homolog \[NRAS\])
* No prior chemotherapy for metastatic disease
* Able to understand and provide written informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy \> 3 months
* Measurable or evaluable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria, i.e. lesions that can be accurately measured in at least one dimension with the longest diameter \>= 20 mm using conventional techniques or \>= 10 mm using spiral computed tomography (CT) scan
* Absolute neutrophil count (ANC) \> l500/ul
* Hemoglobin \> 9g/dL
* Platelets \> 100,000/ul
* Total bilirubin =\< 1.5 times upper limit of normal
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times upper limit of normal
* Alkaline phosphatase \< 2.5 times the upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Creatinine \< 1.5 mg/dL
* Patients genotyped for UGT1A1\*28 polymorphism with \*1/\*1 or \*1/\*28 genotype
* Men and women of childbearing potential must agree to use adequate contraception (double barrier birth control) for the duration of study therapy
* Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential

Exclusion Criteria:

* Patients with both variant alleles (\*28/\*28)
* Patients with any polymorphism in UGT1A1 other than \*1 or \*28 (e.g, \*6)
* Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis
* Patients with specific contraindications to the use of anti-EGFR therapy such as pulmonary fibrosis, interstitial pneumonia history
* Unresolved diarrhea and bowel obstruction
* Active bleeding
* Documented cerebral metastasis
* Serious active infectious disease
* Pregnancy
* Radiotherapy or major surgery within 4 weeks
* Psychiatric illness or social situations that would limit compliance with study requirements
* Presence of previous or concomitant neoplasm with exclusion of in situ cervical cancer
* Patients taking substrates, inhibitors and inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan