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

• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or agree to abstain from sexual intercourse during their participation in the study and for 3 months following completion of their participation
• Patients must have measurable disease
• Histologically documented adenocarcinoma (including the histologic variants of adenocarcinoma) of the colon or rectum
• Patients K-ras status must be wild type (not mutated); K-ras status determination may be based on either primary or metastatic tumor * NOTE: the assay must be performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory
• Patients must have had prior first-line therapy with oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer
• Registration within 42 days of evidence of disease progression
• Performance status 0-1
• Absolute neutrophil count (ANC) >= 1,500/uL
• Hemoglobin >= 9 g/dL
• Platelet >= 75,000/uL
• Serum creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance (measured via 24-hour urine collection) >= 40 mL/minute
• Urine protein/creatinine (UPC) ratio < 0.5 or urine protein =< 1+ on dipstick or routine urinalysis (UA); if UPC >= 0.5 or urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must demonstrate < 1,000 mg of protein in 24 hours to allow participation in the study
• Total bilirubin =< 2.0 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times ULN (or 5.0 x ULN in the setting of liver metastases)
• Albumin within institutional normal range
• International normalized ratio (INR) =< 1.6 (unless receiving anticoagulation therapy); patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin; if receiving warfarin, the patient must have an INR =< 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy)
• No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for this disease; chemotherapy drugs and bevacizumab may be stopped and started as long as no prior disease progression requiring change in chemotherapy agents occurred
• No clinically significant (equivalent to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3-4) bleeding episodes within the past 3 months
• No active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder
• No uncontrolled or poorly controlled hypertension despite standard medical management(e.g., consistently systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 mmHg)
• No major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
• No history of acute arterial thrombotic events within the past 6 months (including cerebrovascular accident [CVA], transient ischemic attack [TIA], myocardial infarction [MI], or unstable angina)
• No brain or central nervous system (CNS) metastases
• No other cancer requiring therapy within the last 3 years (except in situ carcinoma or nonmelanoma skin cancer)
• Patients must not have an acute or subacute intestinal obstruction; no history of bowel obstruction, gastrointestinal (GI) perforation, major abdominal surgery with bowel resection, or perirectal/perianal abscess within 6 months prior to randomization
• Patient must not have a history of inflammatory bowel disease requiring pharmacological and/or surgical intervention within the 12 months prior to randomization
• Patient must not have a known allergy to any of the treatment components