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

Head and Neck Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00601913
• Other study ID #: IRB00004038
• Secondary ID: P30CA012197CCCWF
• Status: Completed
• Phase: Early Phase 1
• Start date: March 2008
• Est. completion date: October 2014

Study information

• Verified date: July 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01588613

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• erlotinib hydrochloride

Genetic:
• protein analysis

• western blotting

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

• liquid chromatography

• mass spectrometry

Procedure:
• neoadjuvant therapy

• therapeutic conventional surgery

Locations

Country	Name	City	State
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response
Secondary	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
Secondary	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
Secondary	Incidence of risk factors for relapse
Secondary	Incidence of adverse effects or significant laboratory changes
Secondary	Any treatment-induced delay of the established date for definitive surgical treatment