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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)


N/A
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

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Trial Information

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)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

Mercedes Porosnicu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Comprehensive Cancer Center of Wake Forest University

Authority:

United States: Institutional Review Board

Study ID:

CDR0000581171

NCT ID:

NCT00601913

Start Date:

March 2008

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096