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