Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy

Inclusion Criteria: * Measurable disease * Histologically confirmed adenocarcinoma of the colon or rectum * K-ras wild type based on either primary or metastatic tumor * Must have received prior first-line therapy comprising oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer * Registration within 42 days since confirmed disease progression * Performance status 0-1 * ANC ≥ 1,500/μL * Platelet count ≥ 75,000/μL * Hemoglobin ≥ 9 g/dL * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min * Urine protein ≤ 1+ on dipstick or routine urinalysis (if ≥ 2+, a 24-hour urine collection must demonstrate \< 1,000 mg of protein) * Total bilirubin ≤ 2.0 mg/dL * AST and ALT ≤ 3.0 times ULN (5.0 times ULN for patients with liver metastases) * INR ≤ 1.6 (≤ 3.0 for patients on warfarin and no active bleeding \[i.e., no bleeding within the past 14 days\]) * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * At least 28 days and no more than 90 days since prior bevacizumab * Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed Exclusion Criteria: * Brain or CNS metastases * Pregnant or nursing * Prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for colorectal cancer * Clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes wi…