Title
A Pilot Window of Opportunity Study of Imatinib in Combination with Cetuximab in Patients with Squamous Cell Carcinomas of the Head and Neck

Description
The goal of this clinical trial is to find if levels of a protein called AXL in tumor cells relate to how tumors respond to cetuximab (CTX) combined with imatinib in participants with head and neck cancer. This interventional study will occur in the time between diagnosis of your cancer and surgery to remove your tumor or radiation or chemoradiation treatment of your primary cancer.

Participants will undergo a research blood draw and a research biopsy as part of the screening process, and will be in this research study for approximately 13 to 16 months.

Objective
Primary Objective
-To determine the proportion of patients with head and neck squamous cell carcinomathat show a response to imatinib plus CTX.
Secondary Objectives
-To further describe the safety and tolerability of the combination of imatinib plus CTX in this window of opportunity trial.
-To estimate the clinical response of the combination of imatinib plus CTX in this window of opportunity trial

Treatment Experimental: Imatinib Cetuximab Combination
Participants will receive two doses of CTX and a minimum of an 8 day (maximum 14 day) course of imatinib prior to definitive surgery or definitive radiation/chemoradiation.
Drug: Cetuximab
Week 1: loading dose of 400mg/m2; Week 2: 250mg/m2
Drug: Imatinib
400 mg orally daily

Key Eligibility 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.

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.

Applicable Disease Sites
Esophagus; Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital