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

Phase

N/A

Condition

Lung Cancer

Skin Cancer

Carcinoma

Treatment

N/A

Clinical Study ID

NCT01588613

CCCWFU 60307

NCI-2009-01255

Ages > 18
Both

Study Summary

This clinical trial is studying how well erlotinib hydrochloride works when given before surgery in treating patients with head and neck cancer that can be removed by surgery. 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of Squamous Cell Carcinoma (SCC)of the Head and Neck: maxillary sinuses, oral cavity, oropharynx, hypopharynx,larynx, skin
Assessed to be candidates for surgical treatment and have an already established datefor surgery with a window of opportunity of at least 15 days
Patients with SCC tumors will be eligible for this protocol only if they haveadditional biopsy tissue already saved in our Tumor Tissue Core Laboratory forresearch purpose or if they agree to have additional biopsies of tumor with adjacentnormal tissue available for molecular studies
Patients will only be eligible for this trial if they have tumor measurable on the CTscan or magnetic resonance imaging (MRI)
No prior radiotherapy or chemotherapy for this tumor
No chemotherapy, biologic therapy or hormonotherapy within the last one year
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) > 1,500/ul
Platelet count > 100,000/ul
Total bilirubin < 1.5
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 2 times theupper limit of normal
Written informed consent must be obtained from all subjects prior to beginningtherapy (subjects should have the ability to understand and be willing to sign awritten informed consent document)

Exclusion

Exclusion Criteria:

Patients with nasopharyngeal carcinoma
Patients receiving any other investigational agents
Patients who received prior treatment with EGFR inhibitors
Subjects with uncontrolled intercurrent illness including, but not limited to,ongoing or active infection or psychiatric illness/social situations that would limitcompliance with study requirements, significant history of uncontrolled cardiacdisease (i.e., uncontrolled hypertension, unstable angina, recent myocardialinfarction [within prior 3 months], uncontrolled congestive heart failure, andcardiomyopathy with decreased ejection fraction)
Subject with a history of interstitial lung disease (e.g., pneumonitis or pulmonaryfibrosis) or evidence of interstitial lung disease on screening chest CT scan
Patients with clinically significant ophthalmologic abnormalities
Pregnant women are excluded; breastfeeding should be discontinued; men enrolled onthis study should understand the risks to any sexual partner of childbearingpotential and should practice an effective method of birth control; subjects who arewomen of childbearing potential and sexually active males must be willing to useeffective contraception while on study
Human immunodeficiency virus (HIV)-positive subjects are excluded from the study

Study Design

July 01, 2008

Study Description

PRIMARY OBJECTIVES:

I. Identify the tissue biomarkers (primarily the level of phosphorylation of individual C-terminal epidermal growth factor receptor [EGFR] tyrosine sites, measured by nano-liquid chromatography-tandem mass spectrometry [LC-MS/MS] and markers of main downstream pathways activation such as phosphor [P]-AKT and phosphor-extracellular signal-regulated kinases [P-ERK], measured by nano-LC-MS/MS and by more clinically standardized immunohistochemistry [IHC]) that best associate with response to neoadjuvant treatment with erlotinib in patients with resectable head and neck squamous cell carcinoma (HNSCC).

II. Determine best correlations between levels (and changes) of different individual biomarkers such as levels of C-terminal EGFR phosphorylation, 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 in squamous cell carcinoma of the head and neck (SCCHN) tissue.

III. Evaluate post-erlotinib up-regulation of different receptors and molecules such as Her 2, 3, platelet-derived growth factor receptor (PDGFR), insulin-like growth factor receptor (IGFR), mammalian target of rapamycin (mTOR), src, aurora kinases, for which there are already specific inhibitors available for clinical studies.

SECONDARY OBJECTIVES:

I. Evaluate efficacy by overall response (OR), safety and tolerability of administration of erlotinib before surgery for patients with operable HNSCC.

II. Evaluate role of fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) scan as a predictor of response to erlotinib.

III. Evaluate the role of PET-computed tomography (CT) in measuring the response to short term treatment with erlotinib.

IV. 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 >= 1year]).

NON-ACTIVELY SMOKING PATIENTS: Patients receive low dose erlotinib hydrochloride orally (PO) once daily (QD) for at least 14 days. At day 15 patients undergo surgical resection of the tumor.

ACTIVELY SMOKING ADULTS: Patients receive high dose erlotinib hydrochloride PO QD 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 (e.g., src and aurora kinases A and B) and confirmed by western blot, protein array, and immunohistochemistry.

After completion of study treatment, patients are followed up at 1 month.

Connect with a study center

University of North Carolina Health Care
Chapel Hill, North Carolina 27599-7600
United States
Site Not Available
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
Active - Recruiting

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