Inclusion Criteria:

1. Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower
⅓), GE junction, or gastric cardia.

2. Clinical stage I, II, or III as assessed by required baseline staging (see Section
7.2). In addition, patients with celiac node involvement (stage IVa) are eligible.

3. Patients must be surgical candidates based on stage and location of disease as well
as other medical conditions and risk factors.

4. Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor)
as defined by FISH (HER2 FISH positivity).

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or
1(Appendix A).

6. Patient must be able to swallow and absorb oral medication.

7. Patients must have an indwelling central venous access catheter.

8. Adequate hematologic function defined as:

- Absolute neutrophil count (ANC) ≥1500/μL

- Hemoglobin (Hgb) ≥9 g/dL

- Platelets ≥100,000/uL

9. Adequate liver function defined as:

- Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 x the
upper limit of normal (ULN)

- Total bilirubin ≤1.5 x ULN

10. Adequate renal function defined as either:

•Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min by the
Cockcroft-Gault method: GRF = (140-age) x (weight/kg) x (0.85 if female) (72 x serum
creatinine mg/dL)

11. Known brain or leptomeningeal metastases.

12. Male patients willing to use adequate contraceptive measures (see Appendix B).

13. Female patients who are not of child-bearing potential (see Appendix B), and female
patients of child-bearing potential who agree to use adequate contraceptive measures
(see Appendix B), who are not breastfeeding, and who have a negative serum or urine
pregnancy test within 72 hours prior to start of treatment.

14. Life expectancy ≥ 12 weeks.

15. Age ≥18 years of age.

16. Willingness and ability to comply with trial and follow-up procedures.

17. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

1. 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.

2. Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.

3. Any other investigational agents within the 28 days prior to day 1 of the study.

4. 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).

5. 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. See Appendix D for a list of prohibited inducers and
inhibitors of CYP3A4 with corresponding washout periods.

6. Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to
starting study drug is not allowed.

7. 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.

8. 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.

9. 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).

10. Poorly controlled or clinically significant atherosclerotic vascular disease
including the following:

- Congestive heart failure (New York Heart Association [NYHA] ≥ Class 3 [See
Appendix C]

- Unstable angina pectoris requiring nitrates within the last 12 months

- Acute myocardial infarction, cerebrovascular accident, or transient ischemic
attack within the last 12 months

- Angioplasty (coronary or vascular) within the last 12 months

- Cardiac or vascular stenting in the past 12 months

- Ventricular arrhythmia requiring medication within the last 12 months

- Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO)

- QTc > 480 ms on screening ECG

11. 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.

12. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis
C (HCV).

13. 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.

14. Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.

15. Inability or unwillingness to comply with study and/or follow-up procedures outlined
in the protocol.