Cetuximab, Docetaxel, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed by Surgery

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. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab, docetaxel, and cisplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase I/II trial is studying the side effects of cetuximab, docetaxel, cisplatin, and radiation therapy and to see how well they work in treating patients with locally advanced esophageal cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin in patients with resectable locally advanced esophageal cancer. Secondary Determine the feasibility and efficacy of this regimen in these patients. Determine the duration of response and patterns of failure in patients treated with this regimen. OUTLINE: This is a multicenter study. Chemoimmunotherapy: Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-3 and docetaxel IV over 1 hour and cisplatin IV over 1 hour once in week 1. Treatment repeats every 3 weeks for 2 courses. Chemoimmunotherapy and radiotherapy: Patients are sequentially assigned to 1 of 2 treatment levels. Treatment level 1: Patients receive cetuximab IV over 1 hour once weekly, cisplatin IV over 1 hour once weekly, and undergo radiotherapy once daily, 5 days a week, in weeks 7-11. Treatment level 2: Patients receive cetuximab, cisplatin, and radiotherapy as in treatment level 1. Patients also receive docetaxel IV over 1-2 hours once weekly in weeks 7-11. Cohorts of 7-20 patients are treated at treatment level 1 or 2 sequentially, as long as no more than 2 of 7 patients experience dose-limiting toxicity (DLT), until the safe treatment level for future study is determined. The safe treatment level is defined as the level at which no more than 2 of 7 and no more than 6 of 20 patients experience DLT. At least 20 patients are treated at the safe treatment level. Surgery: Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and radiotherapy, patients undergo surgery. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.

Official Title
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Cetuximab in Combination With Radiation Therapy and Chemotherapy Prior to Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma. A Multicenter Phase IB-II Trial

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Biological: cetuximab + docetaxel + cisplatin
* Biological: Treatment level 1
* Biological: Treatment level 2
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus Carcinoma of the gastroesophageal junction (i.e., Siewert staging system type I disease) allowed Locally advanced disease Obstructive tumors are considered locally advanced disease Meets 1 of the following staging criteria: T3, N0 disease T1-3, N1 disease T4, N0-1 disease Resectable disease No T4 (unequivocal organ involvement) disease that cannot be resected with curative intent No airway infiltration in case of tumors of the upper third of the thoracic esophagus No cervical esophageal carcinoma No distant metastasis, including stage M1a (celiac node involvement) by fine-needle aspiration or biopsy PATIENT CHARACTERISTICS: WHO performance status 0-1 Creatinine clearance > 60 mL/min Bilirubin normal Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN) AST ≤ 1.5 times ULN Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of study treatment No other malignancy within the past 5 years except nonmelanomatous skin cancer or adequately treated in situ cervical cancer No severe or uncontrolled cardiovascular disease including, but not limited to, any of the following: New York Heart Association class III or IV congestive heart failure Unstable angina pectoris Myocardial infarction within the past 3 months Significant arrhythmias No psychiatric disorder that would preclude study compliance No active uncontrolled infection No serious underlying medical condition that, in the opinion of the investigator, would interfere with study participation (e.g., uncontrolled diabetes mellitus or active autoimmune disease) No peripheral neuropathy > grade 1 No contraindications to corticosteroids No known hypersensitivity to any component of the study drugs PRIOR CONCURRENT THERAPY: No prior chemotherapy No prior radiotherapy to the chest No participation in another clinical trial within the past 30 days No other concurrent experimental drugs or anticancer therapy No concurrent drugs contraindicated for use with the study drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

| Intervention/Treatment |
| --- |
|Biological: cetuximab + docetaxel + cisplatin|Chemoimmunotherapy: Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-3 and docetaxel IV over 1 hour and cisplatin IV over 1 hour once in week 1. Treatment repeats every 3 weeks for 2 courses.|
|Biological: Treatment level 1|Treatment level 1: Patients receive cetuximab IV over 1 hour once weekly, cisplatin IV over 1 hour once weekly, and undergo radiotherapy once daily, 5 days a week, in weeks 7-11.|
|Biological: Treatment level 2|Patients receive cetuximab, cisplatin, and radiotherapy as in treatment level 1. Patients also receive docetaxel IV over 1-2 hours once weekly in weeks 7-11.|
|Procedure: conventional surgery|Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and radiotherapy, patients undergo surgery.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin | Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin | Until treatment ends | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the feasibility and efficacy of the study's regimen | Determine the feasibility and efficacy of this regimen in these patients. | Until trial ends | 
| Determine the duration of response and patterns of failure | Determine the duration of response and patterns of failure in patients treated with this regimen | Until trial ends | 

 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, stage II esophageal cancer, stage III esophageal cancer