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
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|ClinicalTrials.gov Identifier: NCT01107639|
Recruitment Status : Completed
First Posted : April 21, 2010
Last Update Posted : December 11, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Gastroesophageal Junction Esophageal Cancer||Biological: cetuximab Drug: cisplatin Drug: docetaxel Procedure: adjuvant therapy Procedure: neoadjuvant therapy||Phase 3|
- 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.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||297 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multimodal Therapy With and Without Cetuximab in Patients With Locally Advanced Esophageal Carcinoma - An Open-Label Phase III Trial|
|Actual Study Start Date :||May 27, 2010|
|Actual Primary Completion Date :||October 6, 2016|
|Actual Study Completion Date :||December 9, 2018|
Experimental: Additional immunotherapy (cetuximab)
All patients in the experimental arm will be given additional immunotherapy (cetuximab) during cycles 1 and 2, during RT and after surgery.
Loading dose 400 mg/m2 2h infusion Weekly: 250 mg/m2 1h infusion
Other Name: Erbitux
Other Name: Taxotere or generic product
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.
Active Comparator: Without additional immunotherapy
Standard therapy without immunotherapy (cetuximab).
Other Name: Taxotere or generic product
- Progression-free survival (PFS) [ Time Frame: 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
- Progression-free survival after surgery [ Time Frame: from date of surgery to an event as defined in PFS. ]
- Adverse events according to CTCAE version 4.0 and major postoperative complications [ Time Frame: during treatment and follow-up period. ]
- Pathological remission [ Time Frame: Assessed according to the tumor regression model of Mandard ]
- Overall survival [ Time Frame: time from trial randomization to the date of death from any cause ]
- Time to locoregional failure after R0 resection [ Time Frame: from date of surgery to date of first documented loco-regional failure ]
- Time to systemic failure after R0 resection [ Time Frame: from date of surgery to date of first documented systemic failure ]
- In-hospital mortality [ Time Frame: occurring after surgery but while the patient remains in hospital ]
- Time to progression (TTP) [ Time Frame: 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01107639
Show 57 Study Locations
|Study Chair:||Thomas Ruhstaller, MD||Cantonal Hospital of St. Gallen|
|Study Chair:||Michael Stahl, MD||Kliniken Essen-Mitte|