Pilot Feasibility Trial of 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, NO-1 or T1-2, N1 and MO 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