Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

PRIMARY OBJECTIVES: I. Compare the progression free survival (PFS) of the combination of cetuximab and sorafenib to that of cetuximab alone in patients with recurrent, refractory or metastatic squamous cell carcinoma of the head and neck (SCCHN). SECONDARY OBJECTIVES: I. To evaluate the response rate, overall survival (OS) and toxicity of the combination of cetuximab and sorafenib and of cetuximab alone. II. To evaluate the presence of EGFRvIII mutation, increased EGFR gene copy number and activated EGFR gene expression signature, and correlate with clinical parameters (RR, OS and PFS) in the cetuximab alone and cetuximab/sorafenib arms. III. To evaluate whether VEGF receptor family and their ligand expression can predict response to cetuximab/sorafenib. IV. To determine the proteomic profiles in serum and tumors that can predict the response and survival upon the treatment with cetuximab or cetuximab/sorafenib. V. To evaluate the effect of therapy on both general and head and neck specific functionality, symptom burden and QOL. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. (oral placebo closed as of 02/18/2010). ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paraffin embedded tissue samples are collected at baseline for pharmacogenomic studies and blood samples are collected at baseline and for the first 3 courses for research purposes. Quality of life and symptom burden are assessed by Vanderbilt Head and Neck Symptom Survey, FACT-HN, and Fatigue and Pain Inventory questionnaires at baseline, at day 43, and at 3 and 6 months. After completion of study treatment, patients are followed periodically for 3 years.