Trial Information

Pilot Study to Evaluate the Anti-tumor Effect of Erlotinib Administered Before Surgery in Operable Patients With Squamous Cell Carcinoma of the Head and Neck (HNSCC)

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.