A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6).
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TPS5600 Background: Standard treatment for locally advanced SCCHN, chemoradiotherapy (CRT), leads to significant acute and long-term morbidity. The demonstration that EGFR antibody (Ab) therapy improves outcome when added to standard RT (Bonner NEJM 2006) and that altered fractionation RT improves outcome compared to standard RT that is of similar magnitude as CRT (Bourhis Lancet 2006), led to the hypothesis that the combination of the two treatment strategies will improve efficacy compared to standard CRT with good tolerability. Methods: HN.6 is a Canadian phase III randomized study comparing standard RT 70Gy/35 over 7 weeks + cisplatin 100mg/m2 d 1, 22, 43 to accelerated RT 70Gy/35 over 6 weeks + panitumumab (anti EGFR Ab)) 9mg/kg 1 week prior to RT, d15, 36. Key eligibility criteria are: SCC of oral cavity, oropharynx, larynx or hypopharynx; TanyN+M0 or T3-4N0M0; adequate organ function and PS. Primary endpoint is progression free survival (PFS). Secondary endpoints include OS, local PFS, regional PFS, distant metastases, swallowing related QOL, functional swallowing outcomes, and economic evaluation (healthcare utilization, health utilities, indirect costs). Tissue and blood collection will allow biomarker evaluation including HPV status. Real time quality review of RT plans with plan data and radiology archiving will allow future analysis of RT parameters relative to toxicity and patterns of failure. Clinical epidemiological data will be prospectively collected and correlated with biomarkers and outcome. Planned sample size is 320 patients over 3.2 years with 3 more years of follow-up and target hazard ratio = 0.7 (absolute difference in control arm 2 year PFS of 12%, power 80%, 2-tail type 1 error 0.05). If superiority is not demonstrated, noninferiority will be tested. One interim analysis is planned. Conduct to Date: Study activation: Dec 2008 and completed accrual in Nov 2011. In Oct 2011, the DSMC recommended trial continuation. Supported by CCSRI grant 021039 and Amgen Inc. ClinicalTrials.gov: NCT00820248.
