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

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ClinicalTrials.gov Identifier: NCT00601913
Recruitment Status : Completed
First Posted : January 28, 2008
Last Update Posted : August 1, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief 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.


Condition or disease Intervention/treatment Phase
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

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (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)
Actual Study Start Date : March 2008
Primary Completion Date : October 2014
Study Completion Date : October 2014


Arms and Interventions

Arm Intervention/treatment
Experimental: Erlotinib
Erlotinib
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


Outcome Measures

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. Objective response
  2. 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
  3. 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
  4. Incidence of risk factors for relapse
  5. Incidence of adverse effects or significant laboratory changes
  6. Any treatment-induced delay of the established date for definitive surgical treatment

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00601913


Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mercedes Porosnicu, MD Wake Forest University Health Sciences
Principal Investigator: J. D. Browne, MD Wake Forest University Health Sciences
More Information

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT00601913     History of Changes
Obsolete Identifiers: NCT01588613
Other Study ID Numbers: CDR0000581171
P30CA012197 ( U.S. NIH Grant/Contract )
CCCWFU-60307 ( Other Identifier: Comprehensive Cancer Center of WFUHS )
First Posted: January 28, 2008    Key Record Dates
Last Update Posted: August 1, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:
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:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action