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

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with irinotecan hydrochloride- and cisplatin-refractory metastatic esophageal, gastroesophageal junction, or gastric cancer treated with cetuximab, cisplatin, and irinotecan hydrochloride. Secondary Determine the median survival of patients treated with this regimen. Determine the tolerability of this regimen in these patients. Determine the adverse event profiles in patients treated with this regimen. Assess epidermal growth factor receptor expression in tumor tissue from patients treated with this regimen. OUTLINE: This is an open-label, nonrandomized study. Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy at baseline to evaluate epidermal growth factor receptor by immunohistochemistry. After completion of study treatment, patients are followed every 3 months for up to 1 year.

Official Title
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Phase II Trial of Cetuximab Plus Cisplatin and Irinotecan in Patients With Irinotecan and Cisplatin-Refractory Metastatic Esophageal and Gastric Cancer

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: cisplatin
* Drug: irinotecan hydrochloride
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab, Cisplatin, and Irinotecan<br>Cetuximab will be combined with weekly irinotecan and cisplatin. Patients will receive cetuximab 400 mg/m2 on day 1, week 1. Following this loading dose, patients will receive weekly cetuximab 250 mg/m2 (day 8, 15, 22, etc.) until disease progression or unacceptable toxicity. Patients will continue to receive irinotecan and cisplatin weekly on day 1 and day 8, on an every 21 day cycle. The standard maximum doses are irinotecan 65 mg/m2 and cisplatin 30 mg/m2. | Biological: cetuximab<br> <br> Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete and Partial Response Rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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