Erlotinib and Surgery in Treating Patients With Head and Neck Cancer That Can Be Removed by Surgery
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  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.

      Secondary

        -  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.
    

Intervention name(s): erlotinib hydrochloride; protein analysis; western blotting; immunohistochemistry staining method; laboratory biomarker analysis; liquid chromatography; mass spectrometry; neoadjuvant therapy; therapeutic conventional surgery
Intervention type(s): Drug; Genetic; Genetic; Other; Other; Other; Other; Procedure; Procedure
Intervention MeSH terms: Erlotinib Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I squamous cell carcinoma of the oropharynx; stage II squamous cell carcinoma of the oropharynx; stage I squamous cell carcinoma of the larynx; stage II squamous cell carcinoma of the larynx; stage I squamous cell carcinoma of the lip and oral cavity; stage II squamous cell carcinoma of the lip and oral cavity; stage I squamous cell carcinoma of the hypopharynx; stage II squamous cell carcinoma of the hypopharynx; stage I verrucous carcinoma of the larynx; stage I verrucous carcinoma of the oral cavity; stage II verrucous carcinoma of the oral cavity