Combination Chemotherapy and Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (squamous cell carcinoma vs adenocarcinoma) and Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2). Patients are randomized to 1 of 3 treatment arms. For more information please see the "Arms" section which includes a detailed description of the treatment regimens. The primary objective of the study is evaluate the tumor response rate (RR) for each of the regimens in this trial and to select the most promising regimen based on RR for further testing in patients with metastatic esophageal or GE junction adenocarcinoma. The secondary objectives are: 1. To evaluate overall survival (OS) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma. 2. To evaluate progression-free survival (PFS) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma. 3. To evaluate time to treatment failure (TTF) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma. 4. To determine the type and severity of toxicities associated with each of these regimens in the multi-institutional phase II setting. 5. Quantitative immunohistochemistry results will be correlated with objective response rate, overall survival and time to progression. 6. To evaluate the cellular damage (apoptosis) as a result of oxaliplatin. 7. To determine if germline EGFR variants correlate with skin rash in patients treated with cetuximab. 8. To evaluate if a correlation exists between germline EGFR variants and tumor EFGR expression as measured by immunohistochemistry. All subjects must be premedicated with diphenhydramine hydrochloride 50 mg IV (or a similar agent) prior to the first dose of cetuximab in an effort to minimize infusion and hypersensitivity reactions. Premedication is recommended prior to subsequent doses, but the dose of diphenhydramine (or similar agent) may be reduced at the investigator's discretion. More information is detailed in the protocol including a description of the premedication requirements. Patients were closely monitored for treatment-related adverse events. After completion of study treatment, patients are followed periodically for up to 2 years.