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

NCT ID: NCT00601913

Last Updated: 2018-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2014-10-31

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.

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Erlotinib

Erlotinib

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

protein analysis

Intervention Type: GENETIC

western blotting

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

liquid chromatography

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

Interventions

erlotinib hydrochloride

Intervention Type: DRUG

protein analysis

Intervention Type: GENETIC

western blotting

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

liquid chromatography

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mercedes Porosnicu, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

J. D. Browne, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

References

Porosnicu M, O'Brien Cox A, Waltonen JD, Bunch PM, D'Agostino R, Lycan TW, Taylor R, Williams DW 3rd, Chen X, Shukla K, Kouri BE, Walker T, Kucera G, Patwa HS, Sullivan CA, Browne JD, Furdui CM. Early [18]FDG PET/CT scan predicts tumor response in head and neck squamous cell cancer patients treated with erlotinib adjusted per smoking status. Front Oncol. 2022 Aug 30;12:939118. doi: 10.3389/fonc.2022.939118. eCollection 2022.

Reference Type: DERIVED

PMID: 36110959 (View on PubMed)

Other Identifiers

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCCWFU-60307

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00004038

Identifier Type: -

Identifier Source: org_study_id

NCT01588613

Identifier Type: -

Identifier Source: nct_alias