Multimodal Therapy With and Without Cetuximab in Patients With Locally Advanced Esophageal Carcinoma - An Open-Label Phase III Trial
- 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
- 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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS)
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
time from randomization to a defined event.
Thomas Ruhstaller, MD
Kantonsspital St. Gallen