Cetuximab, Docetaxel, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed by Surgery
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

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. 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: 
      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.
    

Intervention name(s): cetuximab + docetaxel + cisplatin; Treatment level 1; Treatment level 2; conventional surgery
Intervention type(s): Biological; Biological; Biological; Procedure
Intervention description(s): 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.; 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.; 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.; Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and radiotherapy, patients undergo surgery.
Intervention MeSH terms: Docetaxel; Cetuximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the esophagus; squamous cell carcinoma of the esophagus; stage II esophageal cancer; stage III esophageal cancer