Erlotinib and Surgery in Treating Patients With Head and Neck Cancer That Can Be Removed by Surgery
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment with erlotinib.
PURPOSE: This clinical trial is studying how well erlotinib works when given before surgery in treating patients with head and neck cancer that can be removed by surgery.
Head and Neck Cancer
Drug: erlotinib hydrochloride
Genetic: protein analysis
Genetic: western blotting
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Early Phase 1
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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 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
- Objective response
- Tumor cell metabolic response measured by PET scan at 4-6 days after beginning of treatment and correlation with tumor response evaluated at the end of treatment by CT scan, PET scan, and direct tumor measurements
- Role of PET/CT scan in evaluating response to short-term treatment with erlotinib hydrochloride and comparison with the same response evaluation performed by CT scan
- Incidence of risk factors for relapse
- Incidence of adverse effects or significant laboratory changes
- Any treatment-induced delay of the established date for definitive surgical treatment
|Study Start Date:||March 2008|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
- 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 hydrochloride.
- Evaluate the role of PET/CT in measuring the response to short-term treatment with erlotinib hydrochloride.
- 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 tumor.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00601913
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Principal Investigator:||Mercedes Porosnicu, MD||Wake Forest University Health Sciences|
|Principal Investigator:||J. D. Browne, MD||Wake Forest University Health Sciences|