Radiation Therapy and Chemotherapy, With or Without Cetuximab, Followed by Surgery in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed by Surgery
Condition: Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays and to kill tumor cells. 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. 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. It is not yet known whether giving radiation therapy
      together with chemotherapy is more effective with or without cetuximab in treating patients
      with esophageal cancer.

      PURPOSE: This randomized phase III trial is studying giving radiation therapy together with
      chemotherapy, with or without cetuximab, followed by surgery in treating patients with
      locally advanced esophageal cancer that can be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the efficacy of neoadjuvant radiochemotherapy comprising docetaxel,
           cisplatin, and radiotherapy in combination with cetuximab followed by surgery and
           adjuvant cetuximab versus neoadjuvant radiochemotherapy comprising docetaxel, cisplatin,
           and radiotherapy followed by surgery in patients with locally advanced esophageal
           carcinoma.

      Secondary

        -  To compare the toxicity of the two therapy arms.

        -  To determine patterns of failure overall and with regard to histology.

        -  To evaluate economic aspects in a subproject and to perform a radiotherapy quality
           assurance program.

      OUTLINE: This is a multicenter study. Patients are stratified according to center, histology
      (adenocarcinoma vs squamous cell carcinoma), primary tumor (T2 vs T3-4), and gender (male vs
      female). Patients are randomized to 1 of 2 treatment arms.

        -  Arm A:

             -  Induction chemotherapy (docetaxel and cisplatin) and concurrent cetuximab Patients
                receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and
                cetuximab IV over 1-2 hours on day 1, 8, and 15. Treatment repeats every 21 days
                for 2 courses.

             -  Chemotherapy (docetaxel and cisplatin), cetuximab, and concurrent radiotherapy
                Beginning in week 7, patients receive cetuximab IV over 1 hour, docetaxel IV over
                30 minutes, cisplatin IV over 1 hour on days 43, 50, 57, 64, and 71 and undergo
                radiotherapy 5 days a week for 5 weeks. Patients then undergo surgery 4-7 weeks
                after completion of radiotherapy.

             -  Adjuvant cetuximab Beginning 3-6 weeks after completion of surgery, patients
                receive cetuximab IV over 1-2 hours once every 2 weeks for a total of 6 doses.

        -  Arm B: Patients receive induction chemotherapy comprising docetaxel IV and cisplatin IV
           for 2 courses as in arm A. Beginning in week 7, patients receive docetaxel IV, cisplatin
           IV, and concurrent radiotherapy for 5 weeks as in arm A. Patients then undergo surgery
           4-7 weeks after completion of radiotherapy.

      After completion of study therapy, patients are followed up at 1 (arm B) or 6 (arm A) months,
      every 3 months for 3 years, and then every 6 months for 2 years.
    

Intervention name(s): cetuximab; cisplatin; docetaxel; adjuvant therapy; neoadjuvant therapy
Intervention type(s): Biological; Drug; Drug; Procedure; Procedure
Intervention description(s): Loading dose 400 mg/m2 2h infusion Weekly: 250 mg/m2 1h infusion; Cisplatin 75 mg/m2 1h infusion d1, 22
Cisplatin 25 mg/m2 1h infusion weekly x5; Docetaxel 75 mg/m2 1h infusion d1, 22
Docetaxel 20 mg/m2 1/2h infusion weekly x5; During the adjuvant phase, all infusions, given every two weeks, will be at a dose of 500mg/m².; During the neoadjuvant phase, the first infusion of cetuximab should be at a dose of 400 mg/m² administered over a period of 2 hours and all subsequent infusions, given weekly, should be of 250 mg/m² over a period of 1 hour, unless any infusion related reaction was observed at a previous infusion. (The maximum infusion rate is 10 mg/min, corresponding to 2 mL/min ready-to-use solution.
Other intervention name(s): Erbitux; Taxotere or generic product
Intervention MeSH terms: Docetaxel; Cetuximab
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIB esophageal cancer; adenocarcinoma of the esophagus; adenocarcinoma of the gastroesophageal junction; squamous cell carcinoma of the esophagus; stage IIIA esophageal cancer; stage IIIB esophageal cancer; stage IIIC esophageal cancer