Randomized Phase III Trial on Postoperative Chemoradiation in Combination With Anti EGFR-Antibody Versus Postoperative Chemoradiation in Head and Neck Squamous Cell Carcinomas (HNSCC) With High Risk of Locoregional Recurrence
- To determine if the addition of concurrently administered panitumumab to standard
adjuvant chemoradiation, with 1 of 2 cisplatin-based regimens, significantly prolongs
disease-free survival of patients with macroscopically completely resected, advanced
squamous cell carcinoma of the hypopharynx, oropharynx, larynx, or oral cavity at high
risk of recurrence.
- To determine if the pre-surgery dose of panitumumab will alter the RNA expression of
several genes and that these changes will provide additional prognostic information
that can be used in future patient management. (Exploratory)
- Measure the differences in RNA expression by RNA microarray and the results analyzed to
create a gene expression classifier that will be checked for outcome prediction by
association with disease free survival and down regulation of the glucose metabolism as
measured by FDG-PET. (Exploratory)
- To create a European biobank of biological samples which can be used for future
research projects in this disease. (Exploratory)
- To predict radiation-induced normal tissue toxicity based on in vitro lymphocyte
apoptosis test and SNPs analysis. (Exploratory)
- To assess the impact of radiation-induced side effects (swallowing dysfunction and
xerostomia) on patient's quality of life.
OUTLINE: This is a multicenter study. Patients are stratified by treatment center,
radiotherapy technique (3D-CRT vs IMRT), chemotherapy regimen (European Organization for
Research and Treatment of Cancer [EORTC]) vs Arbeitsgemeinschaft Radiology Oncology [ARO]
schedule), tumor location (larynx vs oropharynx vs hypopharynx vs oral cavity), pN-stage
(pN0-2 vs pN3), pT-stage (pT1-2 vs pT3-4), margin/extracapsular extension (ECE) status (ECE+
and margin < 5 mm vs ECE- and margin < 5 mm vs ECE+ and margin > 5 mm), biological pre-study
participation (yes vs no), p16 status (positive vs negative vs indeterminable). Patients are
randomized to 1 of 2 treatment arms.
- Arm I (chemoradiotherapy): Within 4-8 weeks of surgery, patients undergo 3D-conformal
or intensity-modulated radiotherapy once daily 5 days a week in weeks 1-7. Patients
also receive concurrent chemotherapy comprising either cisplatin IV over 1-2 hours on
days 1, 22, and 43 (EORTC schedule) OR cisplatin IV over 1-2 hours and fluorouracil IV
over 24 hours on days 1-5 and 29-33 (ARO schedule), in the absence of disease
progression or unacceptable toxicity.
- Arm II (chemoradiotherapy plus panitumumab): Within 4-8 weeks of surgery, patients
undergo 3D-conformal or intensity-modulated radiotherapy and receive concurrent
chemotherapy (EORTC schedule or ARO schedule) as in arm I. Patients also receive
panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43.
Blood samples are collected periodically for biomarker correlative studies and translational
research. Patients complete quality-of-life EORTC questionnaires QLQ-C30, QLQ-HN35, and
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Wilfried Budach, MD
Heinrich-Heine University, Duesseldorf
Europe: not applicable - trial withdrawn