Preoperative Capecitabine, Oxaliplatin, Cetuximab, and Radiation Therapy for Locally Advanced Esophageal Adenocarcinoma

Inclusion Criteria:

• signed informed consent
• patients 18 years of age or older
• biopsy proven, non-recurrent primary adenocarcinoma of the thoracic esophagus or gastro-esophageal junction, disease confined to esophagus and peri-esophageal soft tissue, tumors at the gastroesophageal junction must be limited to no greater than 2 cm into the gastric cardia
• clinical stage T3, N0-1 or T1-2, N1 and M0 or M1a (celiac axis lymph nodes are allowed)
• Karnofsky Performance Status of >60%
• forced expiratory volume at one second (FeV1) must be >1.0 L
• adequate bone marrow reserve equal to or absolute neutrophil count (ANC) > 1500/mcl, total white blood cell count (WBC) > 3000/mcl, platelets >100,000/mcl and hemoglobin > 10.0 g/dl (transfusion permitted)
• adequate hepatic function of direct serum bilirubin < 2 times the upper limit of normal, total bilirubin < 1.5 times the upper limit normal, alanine transaminase (ALT), aspartate transaminase (AST) < 2.5 times the upper limit normal, Alkaline phosphatase < 2.5 times the upper limit normal
• creatinine clearance > 50 ml/min
• female patients of childbearing potential must have a negative serum or urin pregnancy test within 7 days prior to starting therapy

Exclusion Criteria:

• no previous resection or attempted resection of an esophageal cancer
• women who are pregnant or lactating
• life expectancy < 3 months
• serious, uncontrolled concurrent infection(s)
• prior fluoropyrimidine therapy
• prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known Dihydro Pyrimidine Dehydrogenase Deficiency (DPD) deficiency
• treatment for other carcinomas within 5 years, except cured non-melanoma skin and treated in-situ cervical cancer
• history of or evidence of uncontrolled diabetes
• surgical procedure within 6 months of study entry
• participation in any investigational drug study within 4 weeks preceding the start of study treatment
• prior therapy with andy agent that specifically targets the Epidermal Growth Factor Receptor (EGFR) pathway
• prior severe infusion reaction to a monoclonal antibody
• acute hepatitis or known HIV
• clinically significant cardia disease
• evidence of metastases
• other serious uncontrolled medical conditions that the investigator feels might compromise study participation
• major surgery within 4 weeks of the start of treatment without complete recovery
• lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• known, existing uncontrolled coagulopathy
• unwillingness to give written informed consent
• unwillingness to participate or inability to comply with the protocol for the duration of the study
• neuropathy of grade 2 or greater