CCCWFU 60307 - Pilot Study to Evaluate the Anti-tumor Effect of Erlotnib Administered Befor Surgery in Operable Patients With Squamous Cell Carcinoma of the Head and Neck (HNSCC)
- Identify tissue biomarkers (primarily the level of phosphorylation of individual
C-terminal EGFR tyrosine sites, measured by nano-LC-MS/MS and markers of main
downstream pathways activation such as P-AKT and P-ERK, measured by nano-LC-MS/MS and
by more clinically standardized IHC) that best associate with response to neoadjuvant
erlotinib hydrochloride treatment in patients with resectable squamous cell carcinoma
of the head and neck (HNSCC).
- Determine the best correlations between levels and changes of different individual
biomarkers (e.g., levels of C-terminal EGFR phosphorylation and 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
hydrochloride in HNSCC tissue.
- Evaluate post-erlotinib hydrochloride up-regulation of different receptors and
molecules such as HER2 and 3, PDGFR, IGFR, mTOR, src, and aurora kinases, for which
there are already specific inhibitors available for clinical studies.
- Evaluate the efficacy by overall response, safety, and tolerability of erlotinib
hydrochloride before surgery in these patients.
- Evaluate the role of FDG-PET scan as a predictor of response to erlotinib
- Evaluate the role of PET/CT in measuring the response to short-term treatment with
- 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
≥ 1 year]).
- Non-actively smoking patients: Patients receive oral erlotinib hydrochloride 150 mg
once daily for at least 14 days. At day 15 patients undergo surgical resection of the
- Actively smoking patients: Patients receive oral erlotinib hydrochloride 300 mg once
daily 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 such as src and aurora kinases A and B. The results are confirmed by western
blot, protein array, and immunohistochemistry.
After completion of study treatment, patients are followed at 1 month.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Identify tissue biomarkers of EGFR activation and inhibition for which initial values and changes after treatment with erlotinib hydrochloride would best correlate with the objective response of the tumor measured clinically and radiologically
Mercedes Porosnicu, MD
Comprehensive Cancer Center of Wake Forest University
United States: Institutional Review Board
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|