Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas
Condition: Esophageal Cancer
Intervention: Radiation Therapy; Surgery; Tissue Sample
Intervention description: External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks; Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy; For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The interaction of epidermal growth factor receptor (EGFR) inhibitory agents such as
      cetuximab combined with radiation shows promising results. EGFR inhibitory agents also
      enhance radiation-induced apoptosis and inhibit radiation induced damage repair. These
      interactions may represent the principle effects that contribute to the synergy between EGFR
      and radiation.

      This trial will investigate the feasibility and activity of this combination in patients with
      surgically resectable disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the
             esophagus or gastroesophageal junction.

          -  Clinical stage IIA, IIB or III without metastatic disease

          -  Patients must have documented EGFR status or have tumor tissue available for
             assessment of EGFR status by IHC

          -  Patients must be surgical candidates as determined by surgical consult.

          -  Patients must agree to surgery.

          -  ECOG performance status 0 or 2

          -  Absolute neutrophil count (ANC) > 1,000 mm3

          -  Platelet count > 75,000 mm3· Hemoglobin > 10g/dL

          -  Bilirubin < 2.5 X upper limit of normal

          -  AST (SGOT) or ALT (SGPT) < 5.0 ´ upper limit of normal

          -  Creatinine < 2.0 X upper limit of normal

        Exclusion Criteria:

          -  No history of or current brain metastasis.

          -  No significant history of uncontrolled cardiac disease; i.e. uncontrolled
             hypertension, unstable angina, recent myocardial infarction (within prior 6 months),
             uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection
             fraction.

          -  No history of interstitial pneumonitis or pulmonary fibrosis, or suspicion of
             interstitial pneumonitis or pulmonary fibrosis on imaging.

          -  No concurrent chemotherapy not indicated in the study protocol or any other
             investigational agent(s).

          -  No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction

          -  No prior therapy that specifically and directly targets the EGFR pathway (such as
             kinase inhibitors and antibodies directed against the HER family receptors).

          -  No prior severe infusion reaction to a monoclonal antibody.

          -  No major surgery within 28 days prior to being registered for protocol therapy.

          -  No clinically significant infections as judged by the treating investigator.

          -  No acute hepatitis or known HIV.

          -  No other active malignancies.

          -  Negative pregnancy test.

          -  No female patients currently breastfeeding.