Chemotherapy followed by Chemoradiation for the Treatment of Locally Advanced Esophagogastric Cancer

Inclusion Criteria

• Histologically or cytologically confirmed T 3/4 or N+ (> 1 cm in size or fludeoxyglucose F-18 [FDG] avid) Siewart 1-3 gastroesophageal (GE) junction or esophagogastric cancer.
• Age 18 years or older. There will be no upper age restriction
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1,500 cells/mm^3
• Platelets >= 75,000 cells/mm^3
• Total bilirubin =< 1.5 x upper limit of normal OR for patients who have undergone biliary stenting, total bilirubin of =< 2.0 x upper limit of normal OR two down trending values
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x upper limit of normal
• Creatinine =< 1.5 mg/dL OR creatinine clearance >= 30 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• The effects of both radiation therapy and the chemotherapy agents used in this trial are known to be teratogenic. Therefore, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation plus 30 days from the last date of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Female subject of childbearing potential should have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Evidence of metastatic disease as determined by chest CT scan, abdomen/pelvis CT scan (or MRI with gadolinium and/or manganese) within six weeks of study entry. Distant nodal disease is allowed if it is in the radiation port
• Any prior chemotherapy, targeted/biologic therapy, or radiation for treatment of the participant’s esophagogastric cancer
• Treatment of other invasive carcinomas within the last five years with greater than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/ squamous cell carcinoma of the skin are allowed
• Receipt of any other investigational agents within 4 weeks preceding the start of study treatment
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity (e.g. congestive heart failure, symptomatic coronary artery disease and/or cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, or ongoing infection as manifested by fever
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or drug intake
• Pregnant women are excluded from this study because radiation therapy and the chemotherapy agents to be used have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the mother is receiving protocol therapy
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
• No concurrent administration of cimetidine (as it can decrease the clearance of fluorouracil [5-FU]). Another H2-blocker or proton pump inhibitor may be substituted before study entry
• Known, existing uncontrolled coagulopathy
• Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and at least six months earlier). Prior topical fluoropyrimidine use is allowed
• Known hypersensitivity to 5-fluorouracil or known deoxypyridinoline (DPD) deficiency
• History of allergic reaction(s) attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, 5-fluorouracil, irinotecan, or oxaliplatin