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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00601913
First received: January 24, 2008
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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)

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Incidence of risk factors for relapse [ Designated as safety issue: No ]
  • Incidence of adverse effects or significant laboratory changes [ Designated as safety issue: Yes ]
  • Any treatment-induced delay of the established date for definitive surgical treatment [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: March 2008
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, or larynx

    • SCC of the base of the tongue, pharynx, larynx, or hypopharynx are eligible provided additional biopsy tissue has been already saved in the Tumor Tissue Core Laboratory for research purposes
    • SCC of the oral cavity or tonsils are eligible only if they already have or agree to have additional biopsies of tumor with adjacent normal tissue available for molecular studies
  • Candidate for surgical treatment with an established date for surgery with ≥ a 15 day window of opportunity
  • Measurable disease by CT scan or MRI
  • No nasopharyngeal carcinoma

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-2
  • ANC > 1,500/µL
  • Platelet count > 100,000/µL
  • Total bilirubin < 1.5 mg/dL
  • AST/ALT < 2 times upper limit of normal
  • Creatinine < 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • Uncontrolled intercurrent illness including, but not limited to, any of the following:

    • 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, or myocardial infarction within the past 3 months)
    • Uncontrolled congestive heart failure
    • Cardiomyopathy with decreased ejection fraction
  • History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on chest CT scan
  • Clinically significant ophthalmologic abnormalities
  • HIV positivity

PRIOR CONCURRENT THERAPY:

  • More than 1 year since prior chemotherapy, biologic therapy, or hormonal therapy
  • No prior radiotherapy or chemotherapy for this tumor
  • No prior EGFR inhibitors
  • No concurrent grapefruit or grapefruit juice
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601913

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive    336-713-6771      
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Mercedes Porosnicu, MD Comprehensive Cancer Center of Wake Forest University
Principal Investigator: J. D. Browne, MD Wake Forest Baptist Health
  More Information

Additional Information:
No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00601913     History of Changes
Obsolete Identifiers: NCT01588613
Other Study ID Numbers: CDR0000581171, P30CA012197, CCCWFU-60307
Study First Received: January 24, 2008
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Neoplasms by Site
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014