Trial of Preoperative Capecitabine Oxaliplatin Cetuximab & Radiation Therapy for Locally Advanced Esophageal Adenocarcinoma

It is clear that new approaches are needed to improve the therapeutic ratio in esophageal
cancer. This study proposes to evaluate the noval combination of preoperative capecitabine,
oxaliplatin, and cetuximab concurrently with radiation therapy. This will be followed by
esophagectomy 6-9 weeks after the completion of chemoradiation. Followed by further
adjuvant chemotherapy. It is hypothesized that our novel combination of neoadjuvant
capecitabine, oxaliplatin, and cetuximab combined with thoraco-abdominal radiation therapy
will be feasible and result in acceptable toxicity.

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 GE 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)

- Karnosfsky Performance Status of >60%

- FeV1 must be >1.0 L

- adequate bone marrow reserve equal to or ANC > 1500/mcl, total 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, ALT, 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 attemped resection of an esophageal cancer

- women who are pregnant or lactating

- life expectancy < 3 months

- serious, uncontrolled concurrent infection(s)

- prior fluorophrimidine therapy

- prior unanticipated severe reaction to fluoropyrimidine therapy, or known
hypersensitivity to 5-fluorouracil or known 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 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