NCT01107639

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

Multimodal Therapy With and Without Cetuximab in Patients With Locally Advanced Esophageal Carcinoma - An Open-Label Phase III Trial

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 297 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	cetuximab	Loading dose 400 mg/m2 2h infusion Weekly: 250 mg/m2 1h infusion
DRUG	cisplatin	* Cisplatin 75 mg/m2 1h infusion d1, 22 * Cisplatin 25 mg/m2 1h infusion weekly x5
DRUG	docetaxel	* Docetaxel 75 mg/m2 1h infusion d1, 22 * Docetaxel 20 mg/m2 1/2h infusion weekly x5
PROCEDURE	adjuvant therapy	During the adjuvant phase, all infusions, given every two weeks, will be at a dose of 500mg/m².
PROCEDURE	neoadjuvant therapy	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.

Timeline

• Start date: 2010-05-27
• Primary completion: 2016-10-06
• Completion: 2018-12-09
• First posted: 2010-04-21
• Last updated: 2020-10-20

Locations

57 sites across 5 countries: Austria, France, Germany, Hungary, Switzerland