S0415 Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as cetuximab may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.

Detailed Description
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OBJECTIVES: Determine the 6-month overall survival of patients with metastatic adenocarcinoma of the esophagus or gastroesophageal junction treated with cetuximab as second-line therapy. Determine the response rate (confirmed and unconfirmed, complete and partial), time to progression, and time to treatment failure in patients treated with this drug. Determine the toxicity of this drug in these patients. Correlate, preliminarily, gene expression and germline polymorphism of enzymes and genes involved in the epidermal growth factor receptor pathway, DNA repair, and angiogenesis with time to progression, response, overall survival, toxic effects, and time to treatment failure in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on day 1. Treatment repeats once weekly in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months until 3 years from the date of study registration. PROJECTED ACCRUAL: A total of 30-55 patients will be accrued for this study within 6-14 months.

Official Title
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Cetuximab As Second Line Therapy In Patients With Metastatic Esophageal Cancer - Phase II

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Biological: cetuximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of 1 of the following sites: Thoracic esophagus, located > 20 cm* from the incisors Gastroesophageal junction, located ≤ 2 cm into the gastric cardia NOTE: *Tumors located < 26 cm from the incisors must be confirmed by bronchoscopy and negative cytology Disease confined to the esophagus and periesophageal soft tissue Metastatic disease Measurable disease by x-ray, scanning, or physical examination Received exactly 1 prior chemotherapy regimen for metastatic or recurrent disease One prior adjuvant or neoadjuvant chemotherapy regimen allowed if administered at the time of initial diagnosis with localized disease No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Not specified Renal Creatinine ≤ 1.5 times upper limit of normal Other No prior allergic reaction to chimerized or murine monoclonal antibodies No evidence of human anti-mouse antibodies (HAMA) No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No prior cetuximab Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy and recovered No concurrent chemotherapy Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy and recovered Surgery At least 3 weeks since prior thoraco-abdominal surgery and recovered Other No other prior therapy that specifically targets the epidermal growth factor pathway No other concurrent investigational agents

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<br>250 mg/m^2 on days 1, 8, 15, and 22 of every 28-day cycle. | Biological: cetuximab<br>* 1 time Cetuximab 400mg/m2 IV over 120 minutes followed by weekly Cetuximab 250mg/m2 IV over 60 minutes.<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 6 Months | Time to death is measured from date of registration to date of death due to any cause. | every 3 weeks while on treatment, then every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Treatment Failure | Time to treatment failure is measured from date of registration to date of first observation of progressive disease, death due to any cause, symptomatic deterioration, or early discontinuation of treatment. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | every 3 weeks while on treatment | 
| Time to Progression | Progression free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | every 3 weeks while on treatment, then every 3 months for 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, recurrent esophageal cancer, stage IV esophageal cancer