Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas

OUTLINE: This is a multi-center study.

• Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose)
• Cetuximab 250 mg/m2 IV over 60 minutes, day -7.
• Cetuximab 250 mg/m2 IV over 60 minutes, days 1, 8, 15, 22, 29 and 36.
• External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks.
• Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy.
• For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of cetuximab, and at the time of surgery for pathology submission.

Inclusion criteria

• Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction.
• Clinical stage IIA, IIB or III without metastatic disease
• Patients must have documented EGFR status or have tumor tissue available for assessment of EGFR status by IHC
• Patients must be surgical candidates as determined by surgical consult.
• Patients must agree to surgery.
• ECOG performance status 0 or 2
• Absolute neutrophil count (ANC) > 1,000 mm3
• Platelet count > 75,000 mm3· Hemoglobin > 10g/dL
• Bilirubin < 2.5 X upper limit of normal
• AST (SGOT) or ALT (SGPT) < 5.0 ´ upper limit of normal
• Creatinine < 2.0 X upper limit of normal

Exclusion criteria

• No history of or current brain metastasis.
• No significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
• No history of interstitial pneumonitis or pulmonary fibrosis, or suspicion of interstitial pneumonitis or pulmonary fibrosis on imaging.
• No concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
• No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction
• No prior therapy that specifically and directly targets the EGFR pathway (such as kinase inhibitors and antibodies directed against the HER family receptors).
• No prior severe infusion reaction to a monoclonal antibody.
• No major surgery within 28 days prior to being registered for protocol therapy.
• No clinically significant infections as judged by the treating investigator.
• No acute hepatitis or known HIV.
• No other active malignancies.
• Negative pregnancy test.
• No female patients currently breastfeeding.