A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of People With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab (FC-4)

Inclusion Criteria:

• Must consent to be in the study and must have signed and dated IRB-approved consent forms conforming to federal and institutional guidelines for the pre-entry tumor sample submission for central K-RAS testing and for the study treatment
• Must have an ECOG performance status of 0, 1, or 2
• Must have metastatic CRC
• The CRC tumor or metastatic tumor must be K-RAS wild-type as determined by central testing
• Must be documented disease progression during first-line therapy containing both oxaliplatin and bevacizumab
• Most recent treatment regimen must have ended ≥ 21 days prior to randomization, and clinically significant side effects associated with previous therapy must have resolved to ≤ grade 1 with the exception of neuropathy which must have resolved to ≤ grade 2
• Imaging of the chest, abdomen and pelvis with CT scan or MRI must be performed within 3 weeks prior to randomization
• Must have measurable disease, defined as at least one lesion outside a previous RT field that can be accurately measured in at least one dimension as ≥ 20mm with conventional techniques or as ≥ 10mm with 5mm cuts using a spiral CT scan
• Evidence of adequate bone marrow function: ANC ≥ 1200/mm3, hemoglobin ≥ 9g/dL, platelets ≥ 100,000/mm3
• Evidence of adequate hepatic function. If no liver metastases: AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN for the lab. In the presence of liver metastases: AST ≤ 5.0 x ULN, total bilirubin ≤ 1.5 x ULN for the lab
• Serum creatinine must be ≤ 1.5 x ULN for the lab
• Must have a fasting blood glucose < 126mg/dL. Fasting is defined as no caloric intake for at least 8 hours

Exclusion Criteria:

• Life expectancy less than 12 weeks
• Diagnosis of anal or small bowel carcinoma
• Tumor that is considered by the surgeon to be amenable to complete resection
• Previous radiation therapy to > 25% of bone marrow
• Radiation therapy to sites of measurable disease chosen as target lesions
• Radiological evidence and/or clinical signs or symptoms of CNS metastases
• Any of the following conditions and events: uncontrolled hypertension, defined as systolic BP > 150mmHg or diastolic BP > 100 with or without antihypertensive medication (patients with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; NYHA Class III or IV cardiac disease; myocardial infarction within 6 months before randomization; symptomatic arrhythmia; CNS cerebrovascular ischemia (TIA or stroke) within 6 months before randomization
• Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 12 months prior to randomization. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
• Serious or non-healing wound, skin ulcers, or bone fracture
• Any significant bleeding unless the source of bleeding has been resected
• History of bleeding diathesis or coagulopathy (patients on stable anticoagulant therapy are eligible)
• Any evidence of active infection
• Active inflammatory bowel disease
• Grade 3 or 4 diabetes mellitus as defined by NCI's CTCAE v 3.0 pancreatic endocrine: glucose intolerance (patients with diabetes controlled with diet and/or oral medications are eligible)
• Symptomatic interstitial pneumonitis or definitive evidence of interstitial pneumonitis described on CT scan or chest x-ray in asymptomatic patients
• Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study
• Previous hypersensitivity reaction to monoclonal antibodies
• Previous treatment with irinotecan, cetuximab, or any agent specifically targeting IGF receptors
• Treatment with an investigational drug within 30 days prior to randomization
• Pregnancy or lactation at the time of patient entry
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements