Use of Cetuximab for Unresectable or Metastatic Esophageal and Gastric Cancer
Condition: Esophageal Cancer; Gastric Cancer; Neoplasm Metastasis
MeSH terms: Neoplasm Metastasis; Stomach Neoplasms; Esophageal Neoplasms
Intervention: Cetuximab
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Esophageal Cancer; Gastric Cancer; Metastatic Esophageal Cancer; Metastatic Gastric Cancer; Cetuximab; Metastatic Esophageal and Gastric Cancer

Summary:

      Purpose: There remains a great need for novel therapeutic agents and treatment strategies for
      advanced esophagogastric cancer. Preclinical and clinical studies have demonstrated increased
      EGFR expression in a significant proportion of both esophageal and gastric carcinomas.
      Inactivation of EGFR through use of a monoclonal antibody in preclinical models has resulted
      in inhibition of tumor growth. Agents designed to block the EGFR pathway have demonstrated
      disease control among previously treated patients with metastatic esophageal and gastric
      cancer. The proposed mechanism of action for cetuximab is its ability to effectively disrupt
      EGFR-mediated signal transduction pathways that ultimately leads to halting cell cycle
      progression, induces apoptosis, and also inhibits processes important for tumor growth, such
      as cell invasion and angiogenesis.
    

Eligibility criteria:

        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.