Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

Inclusion Criteria:

• Pathologically confirmed primary adenocarcinoma of the esophagus meeting the following criteria:

  • Involvement of mid (up to 25 cm), distal, or esophagogastric junction

    • Involvement of the stomach up to 5 cm allowed
    • Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula

  • Stage T1, N1-2 or T2-3, N0-2 disease by chest, abdominal, or pelvic CT scan or whole-body PET/CT scan

    • No T1,N0 or T4 disease
    • No metastatic disease
  • Regional adenopathy including para-esophageal, gastric, gastrohepatic, and celiac (≤ 2 cm) nodes allowed
  • No cervical esophageal or proximal esophageal (15-24 cm) carcinoma
• Intent to submit tissue for central HER2 testing
• Must have undergone endoscopy with biopsy
• HER2-overexpressing adenocarcinoma of the esophagus
• Disease must be encompassed in 1 radiotherapy field
• Able to undergo curative resection within 56 days after completion of chemoradiation
• No evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
• Zubrod performance status 0-2
• ANC ≥ 1,500 cells/mm³
• Platelet count ≥100,000 cells/mm³
• Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hb ≥ 8.0 g/dL allowed)
• Creatinine ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST ≤ 3.0 times ULN
• LVEF normal
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for ≥ 60 days after completion of chemotherapy or trastuzumab
• No prior invasive malignancy except non-melanomatous skin cancer or curatively treated carcinoma in situ of the breast, oral cavity, or cervix with no evidence of disease within the past 2 years
• No medical contraindications to esophagectomy
• No prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
• No history of congestive heart failure

• No severe or active comorbidity defined as any of the following:

  • Unstable angina within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics

  • AIDS or immunocompromised patients

    • HIV testing is not required

• No prior systemic chemotherapy for esophageal cancer

  • Prior chemotherapy for a different cancer allowed
• No prior radiotherapy for esophageal cancer or prior chest radiotherapy
• No prior anthracycline or taxane
• No prior therapy with any agent targeting the HER2 pathway or HER1 (EGFR) pathway
• No prior trastuzumab
• No concurrent intensity-modulated radiotherapy
• No other concurrent radiotherapy
• No other concurrent investigational agents
• No other concurrent cytotoxic agents