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

Inclusion Criteria:

Must consent to be in the study and must have signed and dated Institutional Review Board (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 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Must have metastatic CRC
The CRC tumor or metastatic tumor must be v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene (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 computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 3 weeks prior to randomization
Must have measurable disease, defined as at least 1 lesion outside a previous radiation therapy (RT) field that can be accurately measured in at least 1 dimension as ≥20 millimeters (mm) with conventional techniques or as ≥10mm with 5mm cuts using a spiral CT scan
Evidence of adequate bone marrow function: absolute neutrophil (ANC) ≥1200 cubed millimeters (mm³), hemoglobin ≥9 grams per deciliter (g/dL), platelets ≥100,000 mm³
Evidence of adequate hepatic function. If no liver metastases: aspartate aminotransferase (AST) ≤2.5 times (x) upper limit of normal (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 <126 milligrams/deciliter (mg/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 RT to >25% of bone marrow
RT to sites of measurable disease chosen as target lesions
Radiological evidence and/or clinical signs or symptoms of central nervous system (CNS) metastases
Any of the following conditions and events: uncontrolled hypertension, defined as systolic blood pressure (BP) >150 millimeters of mercury (mmHg) or diastolic BP >100 mmHg with or without antihypertensive medication (participants with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; New York Heart Association (NYHA) Class III or IV cardiac disease; myocardial infarction (MI) within 6 months before randomization; symptomatic arrhythmia; CNS cerebrovascular ischemia [transient ischemic attack (TIA) or stroke] within 6 months before randomization
Other malignancies unless the participant is considered to be disease-free and has completed therapy for the malignancy ≥12 months prior to randomization. Participants 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 (participants on stable anticoagulant therapy are eligible)
Any evidence of active infection
Active inflammatory bowel disease
Grade 3 or 4 diabetes mellitus as defined by National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 pancreatic endocrine: glucose intolerance (participants 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 participants
Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study
Previous hypersensitivity reaction to monoclonal antibodies
Previous treatment with irinotecan, cetuximab, or any agent specifically targeting insulin-like growth factor (IGF) receptors
Treatment with an investigational drug within 30 days prior to randomization
Pregnancy or lactation at the time of participant entry
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the participant from meeting the study requirements