Pilot Study of Imatinib Cetuximab Combo for H & N Cancer

Inclusion Criteria: Age > 18 years at the time of consent. Histological confirmation of squamous cell carcinoma of the head and neck. For those patients with oropharyngeal cancer, subjects must have either HPV-negative status by p16 expression or HPV-DNA Expression. HPV-positive status by p16 expression AND a >10 pack year smoking history. Subjects must be appropriate candidates for definitive curative intent treatment, either via surgical resection, definitive radiation therapy alone, or definitive concurrent chemoradiation therapy. For the screening research biopsy, subjects must have sufficient tumor volume (approximately 10 cc) to accommodate at minimum 2-3 core samples for the research biopsy. For the post-treatment (CTX/Imatinib) research biopsy, subjects who are scheduled to receive definitive radiation therapy (+/- concurrent chemotherapy) are required to have sufficient tumor volume to accommodate at minimum 2-3 core samples for the research biopsy. Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration. Exclusion Criteria: Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of the head and neck, or salivary gland tumors are excluded from this study. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol. Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 8 weeks earlier (alopecia and fatigue excluded). Clinical significance to be determined by the study investigator. Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Subjects who are receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or CTX.