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 within the past 3 months
* Active infection
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Symptomatic or poorly controlled cardiac arrhythmia
* Uncontrolled thrombotic or hemorrhagic disorder
* Uncontrolled or poorly controlled hypertension despite standard medical management (e.g., consistently systolic BP \> 160 mm Hg and diastolic BP \> 90 mm Hg)
* Acute arterial thrombotic events within the past 6 months, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina
* Other cancer requiring therapy within the past 3 years except in situ carcinoma or nonmelanoma skin cancer
* Acute or subacute intestinal obstruction
* History of inflammatory bowel disease requiring pharmacological and/or surgical intervention within the past 12 months
* Known allergy to any of the treatment components
* Major surgery within the past 28 days
* Subcutaneous venous access device placement within the past 7 days