Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer

Inclusion Criteria:

* Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower ⅓), GE junction, or gastric cardia.
* Clinical stage I, II, or III as assessed by required baseline staging. In addition, patients with celiac node involvement (stage IVa) are eligible.
* Patients must be surgical candidates based on stage and location of disease as well as other medical conditions and risk factors.
* Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as defined by FISH (HER2 FISH positivity).
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
* Patient must be able to swallow and absorb oral medication.
* Patients must have an indwelling central venous access catheter.
* Adequate hematologic, renal, and hepatic function:
* Known brain or leptomeningeal metastases.
* Male patients willing to use adequate contraceptive measures.
* Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
* Life expectancy ≥ 12 weeks.
* Age ≥18 years of age.
* Willingness and ability to comply with trial and follow-up procedures.
* Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

* Patients with evidence of distant metastases are ineligible, as are patients who are not potential surgical candidates based on location or extent of local disease. Patients with celiac nodal disease (Stage IVa) will be allowed on study.
* Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.
* Any other investigational agents within the 28 days prior to day 1 of the study.
* Known active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
* Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
* Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to starting study drug is not allowed.
* Ongoing treatment with full-dose warfarin or its equivalent. Prophylactic treatment with 1 mg daily of warfarin and/or low molecular weight heparin is allowed.
* History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a novel regimen, or that might affect interpretation of the results of this study or render the subject at high-risk for treatment complications.
* Active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
* Poorly controlled or clinically significant atherosclerotic vascular disease
* A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
* Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
* Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
* Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.