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

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.

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