Cetuximab, Cisplatin, and Irinotecan in Treating Patients With Metastatic Esophageal Cancer, Gastroesophageal Junction Cancer, or Gastric Cancer That Did Not Respond to Previous Irinotecan and Cisplatin
Condition: Esophageal Cancer; Gastric Cancer
MeSH terms: Stomach Neoplasms; Esophageal Neoplasms
Intervention: cetuximab; cisplatin; irinotecan hydrochloride; immunohistochemistry staining method; laboratory biomarker analysis; biopsy
Intervention MeSH terms: Irinotecan; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the esophagus; squamous cell carcinoma of the esophagus; recurrent esophageal cancer; recurrent gastric cancer; adenocarcinoma of the stomach; stage IV esophageal cancer; stage IV gastric cancer

Summary:

      RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth
      of tumor cells by blocking some of the enzymes needed for their growth. Drugs used in
      chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab
      together with cisplatin and irinotecan may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin
      and irinotecan works in treating patients with metastatic esophageal cancer, gastroesophageal
      junction cancer, or gastric cancer that did not respond to previous irinotecan and cisplatin.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed diagnosis of 1 of the following:

               -  Adenocarcinoma or squamous cell carcinoma of the esophagus

               -  Adenocarcinoma of the gastroesophageal junction

               -  Adenocarcinoma of the stomach

          -  Metastatic disease

          -  Measurable disease by diagnostic CT scan or MRI

          -  Failed prior treatment with cisplatin and irinotecan hydrochloride, defined by the
             following:

               -  Radiographic progression within 12 weeks* from the last dose of prior cisplatin
                  and irinotecan hydrochloride, administered either as adjuvant or neoadjuvant
                  therapy, OR as therapy for metastatic disease NOTE: *Prior irinotecan
                  hydrochloride and cisplatin must have been administered within the past 12 weeks;
                  other chemotherapy regimens may have been administered between the time of
                  disease progression or prior irinotecan hydrochloride/cisplatin and study entry

          -  Pathologic tissue available for immunohistochemistry (IHC) staining for the epidermal
             growth factor receptor (EGFR)

               -  Positive or negative EGFR by IHC allowed

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

          -  Life expectancy > 3 months

          -  WBC ≥ 3,000/mm³

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9 g/dL

          -  Bilirubin normal

          -  AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases
             are present)

          -  Creatinine ≤ 2.0 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No prior severe infusion reaction to a monoclonal antibody

          -  No history of allergic reactions to compounds of similar chemical or biologic
             composition to irinotecan hydrochloride, cisplatin, or other study agents

          -  No prior intolerance to irinotecan hydrochloride or cisplatin despite prior dose
             attenuations

          -  No uncontrolled illness including, but not limited to, any of the following:

               -  Ongoing or active infection requiring parenteral antibiotics

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Uncontrolled hypertension

               -  Clinically significant cardiac arrhythmia

               -  Myocardial infarction within the past 6 months

               -  HIV infection

               -  Psychiatric illness or social situations that would preclude study compliance

          -  No history of Gilbert's disease

          -  No medical condition or reason that would preclude study treatment

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  More than 3 weeks since prior chemotherapy or radiotherapy and recovered

          -  No more than 2 prior treatment regimens for metastatic disease

          -  No prior therapy specifically and directly targeting the epidermal growth factor
             receptor pathway

          -  No prior anticancer murine or chimeric monoclonal antibody therapy

               -  Prior humanized monoclonal antibody therapy allowed

          -  No concurrent antiseizure medications known to affect the metabolism of irinotecan
             hydrochloride, including phenytoin or phenobarbital

          -  No other concurrent investigational agents

          -  No other concurrent anticancer agents or therapies