A Phase II Trial of Cetuximab in Unresectable or Metastatic Esophageal and Gastric Carcinoma

Inclusion Criteria:

- Histologically confirmed, unresectable or metastatic stage IV esophageal or gastric
adenocarcinoma. Tumors with squamous cell differentiation, including those with a
mixture of squamous and adenomatous differentiation, are excluded.

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria,
greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT)
scan or greater than or equal to 2 cm by other radiographic technique. Disease in an
irradiated field as only site of measurable disease is acceptable if there has been a
clear progression of the lesion.

- Patients must have at least one paraffin block or twenty unstained slides available
for analysis of epidermal growth factor receptor (EGFR) status.

- Treatment with 1-2 prior chemotherapy regimens given in the metastatic setting for
unresectable or metastatic esophageal or gastric carcinoma.

- ECOG performance status 0-2.

- Life expectancy greater or equal to 12 weeks.

- Age 18 years or older.

- Ability to sign an informed consent document.

- Neutrophils greater than or equal to 1,000/mm3.

- Platelets greater than or equal to 75,000/mm3.

- Serum bilirubin less than or equal to 2.0 mg/dl.

- Serum creatinine less than or equal to 1.5 mg/dl.

- Aspartate aminotransferase (AST or SGOT) less than or equal to 2.5 x upper
institutional normal limit.

Exclusion Criteria:

- Pregnant or lactating women. Women of childbearing potential must have a negative
serum or urine pregnancy test within 14 days of initiation of therapy. Men and women
of reproductive potential may not participate unless they have agreed to use an
effective contraceptive method while in this study.

- Subjects should have no other active malignancy other than non-melanoma skin cancer
or in-situ cervical carcinoma. A resected cancer (other than in-situ carcinoma) must
have demonstrated no evidence of recurrence for at least 3 years.

- Subjects should not have a significant history of cardiac disease, i.e., uncontrolled
hypertension; unstable angina; congestive heart failure; myocardial infarction less
than 6 months prior to registration; or serious uncontrolled cardiac arrhythmia.

- Subjects must not have received prior cetuximab or other therapy that specifically
and directly targets the EGFR pathway. Prior therapy with bevacizumab is permissible.

- Subjects must not have experienced prior severe infusion reaction to a monoclonal
antibody.

- Subjects must not have received any chemotherapy regimen or radiation therapy within
28 days prior to study entry.

- Patients must have completed any major surgery 4 weeks or any minor surgery 2 weeks
prior to the first infusion of cetuximab. Patients must have fully recovered from
the procedure.

- No concurrent use of chemotherapy, radiation, or other investigational agents is
allowed while participating in this study.