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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00601913
First received: January 24, 2008
Last updated: October 28, 2014
Last verified: October 2014

January 24, 2008
October 28, 2014
March 2008
October 2014   (final data collection date for primary 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 [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00601913 on ClinicalTrials.gov Archive Site
  • Objective response [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Incidence of risk factors for relapse [ Designated as safety issue: No ]
  • Incidence of adverse effects or significant laboratory changes [ Designated as safety issue: Yes ]
  • Any treatment-induced delay of the established date for definitive surgical treatment [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Erlotinib and Surgery in Treating Patients With Head and Neck Cancer That Can Be Removed by Surgery
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)

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.

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.

Interventional
Phase 0
Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
25
Not Provided
October 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00601913
CDR0000581171, P30CA012197, CCCWFU-60307
Yes
Comprehensive Cancer Center of Wake Forest University
Comprehensive Cancer Center of Wake Forest University
National Cancer Institute (NCI)
Principal Investigator: Mercedes Porosnicu, MD Comprehensive Cancer Center of Wake Forest University
Principal Investigator: J. D. Browne, MD Wake Forest Baptist Health
Comprehensive Cancer Center of Wake Forest University
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP