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
- Conditions
- Adenocarcinoma of the Gastroesophageal JunctionEsophageal Cancer
- Interventions
- Biological: cetuximabProcedure: adjuvant therapyProcedure: neoadjuvant therapy
- Registration Number
- NCT01107639
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 297
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Additional immunotherapy (cetuximab) cetuximab All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery. Additional immunotherapy (cetuximab) neoadjuvant therapy All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery. Additional immunotherapy (cetuximab) docetaxel All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery. Additional immunotherapy (cetuximab) adjuvant therapy All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery. Without additional immunotherapy docetaxel Standard therapy without immunotherapy (cetuximab). Additional immunotherapy (cetuximab) cisplatin All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery. Without additional immunotherapy cisplatin Standard therapy without immunotherapy (cetuximab).
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) time from randomization to a defined event. time from randomization to one of the following events, whichever comes first:
* Tumor progression at any time (progression of primary tumor or local lymph nodes, appearance of new lesions)
* Recurrence at local, regional or distant site after surgery
* Death from any cause
- Secondary Outcome Measures
Name Time Method Progression-free survival after surgery from date of surgery to an event as defined in PFS. Adverse events according to CTCAE version 4.0 and major postoperative complications during treatment and follow-up period. Pathological remission Assessed according to the tumor regression model of Mandard Overall survival time from trial randomization to the date of death from any cause Time to locoregional failure after R0 resection from date of surgery to date of first documented loco-regional failure Time to systemic failure after R0 resection from date of surgery to date of first documented systemic failure In-hospital mortality occurring after surgery but while the patient remains in hospital Time to progression (TTP) Time to progression is defined as time from randomization to one of the following events, whichever comes first: - Tumor progression at any time. - Recurrence at local, regional or distant site after surgery. - Death due to tumor
Trial Locations
- Locations (57)
Landeskrankenhaus
🇦🇹Feldkirch, Austria
Universitätsklinik für Innere Medizin I
🇦🇹Innsbruck, Austria
Krankenhaus Barmherzige Schwestern Linz
🇦🇹Linz, Austria
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹Linz, Austria
Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Universitätsklinik für Innere Medizin
🇦🇹Wien, Austria
Hôpital Avicenne
🇫🇷Bobigny, France
Centre Hospitalier Général
🇫🇷Béziers, France
Hôtel Dieu Estaing
🇫🇷Clermont Ferrand, France
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