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.