Phase II Study of Irinotecan and Panitumumab

Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of locally recurrent or metastatic adenocarcinoma of the esophagus which is incurable with standard therapy. * Patients must have measurable disease outside a previous radiation port, or which has developed in the port since the conclusion of radiation and is biopsy-proven to be recurrent cancer. * One prior chemotherapy regimen for metastatic disease, with the exception of prior irinotecan or panitumumab. * Prior radiation therapy to no more than 20% of the bone marrow is allowed. No treatment with wide field radiation within 4 weeks of entry onto this study. * Full recovery from the effects of any prior surgery. * Man or woman \>18 years of age. * ECOG performance status \<2 (Karnofsky \>60%) * Life expectancy of \>3 months * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 9.0 g/dL * Creatinine \< or = to 1.5 mg/dL * Creatinine clearance \> or = to 50 mL/min calculated by the Cockcroft-Gault method as follows: * Male creatinine clearance = (140 - age) x (weight in Kg) / (serum Cr x 72) * Female creatinine clearance = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72) * Aspartate aminotransferase (AST) \< or = to 3 x ULN (if liver metastases less than or equal to 5 x ULN) * Alanine aminotransferase (ALT) \< or = to 3 x ULN (if liver metastases less than or equal to 5 x ULN) * Total bilirubin \< or = to 1.5 x ULN * Magnesium ≥ lower limit of normal * Potassium \> or = to lower limit of normal * Because the effects of irinotecan and panitumumab on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Exclusion Criteria: * History or known presence of central nervous system (CNS) metastases unless CNS metastases have been irradiated and are stable. * History of another primary cancer, except: * Curatively treated in situ cervical cancer * Curatively resected non-melanoma skin cancer * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for greater than or equal to 5 years prior to enrollment * Pre-existing peripheral neuropathy \> grade 1. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or irinotecan. * Patients receiving any medications or substances that are established or probable inhibitors or inducers of P450 3A4 are ineligible. * Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) * Radiotherapy \< or = to 14 days prior to enrollment. * Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (or small molecules for Phase I studies) (eg, bevacizumab)\< or = to 30 days before enrollment * Subjects requiring chronic use of immunosuppressive agents (eg, methotrexate, cyclosporine) * Any investigational agent or therapy \< or = to 30 days before enrollment * Prior therapy with Irinotecan or panitumumab. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or any evidence of interstitial lung disease on baseline chest CT scan * History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results. * Women who test positive for serum or urine pregnancy test \< 72 hours before randomization or is breast feeding * Known positive test(s) for acute or chronic active hepatitis B infection * Major surgery within 28 days or minor surgery within 14 days of study enrollment * Men or women of child-bearing potential (women who are post-menopausal \< 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during treatment and for six months after the last investigational product(s) administration * Any underlying condition which in the opinion of the principal investigator will interfere with safety or with compliance with the study.