A Phase 2, Randomized, Double Blind, Placebo Controlled Study of AMG 386 in Combination with FOLFIRI in Subjects with Previously Treated Metastatic Colorectal Carcinoma

- Histologically confirmed adenocarcinoma of the colon or rectum in patients who are presenting with metastatic disease - One and only one prior chemotherapy regimen for metastatic disease consisting of the combination of a fluoropyrimidine-based chemotherapy and an oxaliplatin-based chemotherapy. Prior adjuvant chemotherapy used prior to the onset of metastatic disease is permitted - At least one uni dimensionally measurable lesion per modified RECIST criteria. All sites of disease must be evaluated <= 28 days before randomization - Radiographically documented disease progression per modified RECIST criteria either while receiving or <= 6 months after the last dose of prior chemotherapy regimen for metastatic disease - ECOG performance status of 0 or 1 - Man or woman >= 18 years of age - Adequate end organ assessments by laboratory studies (hematological and chemistries) - Life expectancy >= 3 months

- Exclude subjects with a history of prior malignancy, except: • Malignancy treated with curative intent and with no known active disease present for >= 3 years before enrollment and felt to be at low risk for recurrence by treating physician • Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease •Adequately treated cervical carcinoma in situ without evidence of disease •Prostatic intraepithelial neoplasia without evidence of prostate cancer - Prior irinotecan therapy - Systemic chemotherapy, hormonal therapy, or immunotherapy <= 21 days prior to randomization - Experimental or approved proteins/antibodies (eg, bevacizumab) <= 30 days prior to randomization - Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent - Known allergy or hypersensitivity to irinotecan, 5 FU (known dihydropyrimidine dehydrogenase deficiency) or leucovorin - Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as >= CTC grade 2 [CTCAE version 3.0])