Erlotinib Hydrochloride and Surgery in Treating Patients With Head and Neck Cancer That Can Be Removed By Surgery

PRIMARY OBJECTIVES:

I. Identify the tissue biomarkers (primarily the level of phosphorylation of individual
C-terminal epidermal growth factor receptor [EGFR] tyrosine sites, measured by nano-liquid
chromatography-tandem mass spectrometry [LC-MS/MS] and markers of main downstream pathways
activation such as phosphor [P]-AKT and phosphor-extracellular signal-regulated kinases
[P-ERK], measured by nano-LC-MS/MS and by more clinically standardized immunohistochemistry
[IHC]) that best associate with response to neoadjuvant treatment with erlotinib in patients
with resectable head and neck squamous cell carcinoma (HNSCC).

II. Determine best correlations between levels (and changes) of different individual
biomarkers such as levels of C-terminal EGFR phosphorylation, recruited adaptors and markers
of downstream pathways activation, in order to evaluate the mechanisms of EGFR pathway
activation in HNSCC and mechanisms of EGFR pathway inhibition by erlotinib in squamous cell
carcinoma of the head and neck (SCCHN) tissue.

III. Evaluate post-erlotinib up-regulation of different receptors and molecules such as Her
2, 3, platelet-derived growth factor receptor (PDGFR), insulin-like growth factor receptor
(IGFR), mammalian target of rapamycin (mTOR), src, aurora kinases, for which there are
already specific inhibitors available for clinical studies.

SECONDARY OBJECTIVES:

I. Evaluate efficacy by overall response (OR), safety and tolerability of administration of
erlotinib before surgery for patients with operable HNSCC.

II. Evaluate role of fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) scan as a
predictor of response to erlotinib.

III. Evaluate the role of PET-computed tomography (CT) in measuring the response to short
term treatment with erlotinib.

IV. Evaluate incidence of risk factors for relapse in the surgical pathology specimens.

OUTLINE: Patients are grouped according to smoking status (non-actively smoking [not
smoking, smoking an average of < 10 cigarettes daily, or smoking for < 1 year prior to
enrollment] vs actively smoking [smoking an average of >= 10 cigarettes daily and smoking
for >= 1year]).

NON-ACTIVELY SMOKING PATIENTS: Patients receive low dose erlotinib hydrochloride orally (PO)
once daily (QD) for at least 14 days. At day 15 patients undergo surgical resection of the
tumor.

ACTIVELY SMOKING ADULTS: Patients receive high dose erlotinib hydrochloride PO QD for at
least 14 days. At day 15 patients undergo surgical resection of the tumor.

Patients undergo biopsies at baseline and after completion of study treatment. Tissue
samples are analyzed by nano-liquid chromatography and mass spectrometry (nano-LC-MS/MS) for
markers of activation and inhibition of different EGFR downstream pathways (PKC, c-Cbl,
P-Erk, P-Akt, P-RAF, src, STAT3 and 5, cyclin D1, and D3, p21 and p27, c-fos, E-cadherin,
vimentin) and correlative up-regulated receptors (Her 2, Her 3, Cox-2, IGF, VEGF, PDGFR) or
other kinases (e.g., src and aurora kinases A and B) and confirmed by western blot, protein
array, and immunohistochemistry.

After completion of study treatment, patients are followed up at 1 month.

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of Squamous Cell Carcinoma (SCC)
of the Head and Neck: maxillary sinuses, oral cavity, oropharynx, hypopharynx,
larynx, skin

- Assessed to be candidates for surgical treatment and have an already established date
for surgery with a window of opportunity of at least 15 days

- Patients with SCC tumors will be eligible for this protocol only if they have
additional biopsy tissue already saved in our Tumor Tissue Core Laboratory for
research purpose or if they agree to have additional biopsies of tumor with adjacent
normal tissue available for molecular studies

- Patients will only be eligible for this trial if they have tumor measurable on the CT
scan or magnetic resonance imaging (MRI)

- No prior radiotherapy or chemotherapy for this tumor

- No chemotherapy, biologic therapy or hormonotherapy within the last one year

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) > 1,500/ul

- Platelet count > 100,000/ul

- Total bilirubin < 1.5

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 2 times the
upper limit of normal

- Written informed consent must be obtained from all subjects prior to beginning
therapy (subjects should have the ability to understand and be willing to sign a
written informed consent document)

Exclusion Criteria:

- Patients with nasopharyngeal carcinoma

- Patients receiving any other investigational agents

- Patients who received prior treatment with EGFR inhibitors

- Subjects with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection or psychiatric illness/social situations that would limit
compliance with study requirements, significant history of uncontrolled cardiac
disease (i.e., uncontrolled hypertension, unstable angina, recent myocardial
infarction [within prior 3 months], uncontrolled congestive heart failure, and
cardiomyopathy with decreased ejection fraction)

- Subject with a history of interstitial lung disease (e.g., pneumonitis or pulmonary
fibrosis) or evidence of interstitial lung disease on screening chest CT scan

- Patients with clinically significant ophthalmologic abnormalities

- Pregnant women are excluded; breastfeeding should be discontinued; men enrolled on
this study should understand the risks to any sexual partner of childbearing
potential and should practice an effective method of birth control; subjects who are
women of childbearing potential and sexually active males must be willing to use
effective contraception while on study

- Human immunodeficiency virus (HIV)-positive subjects are excluded from the study