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