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

This study is currently recruiting participants.
Verified July 2013 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT01588613
First received: April 17, 2012
Last updated: July 29, 2013
Last verified: July 2013

April 17, 2012
July 29, 2013
July 2008
July 2014   (final data collection date for primary outcome measure)
Correllation of tissue biomarkers with response to erlotinib [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
Estimate the correlation of the change in each biomarker with level of response, perform a series of 2-sample t-tests to determine which biomarkers exhibited a significant difference between responders and non-responders, the investigators will also examine whether the baseline measures of individual biomarkers are significantly predictive of subsequent response status. To do this the investigators will assess the correlation of the baseline biomarker and subsequent response outcome and perform 2-sample t-tests comparing the mean baseline biomarker values between responders and non-responders.
Correllation of tissue biomarkers with response to erlotinib [ Time Frame: day 1 to day 15 ] [ Designated as safety issue: No ]
Estimate the correlation of the change in each biomarker with level of response, and perform a series of 2-sample t-tests to determine which biomarkers exhibited a significant difference between responders and non- responders, we will also examine whether the baseline measures of individual biomarkers are significantly predictive of subsequent response status. To do this we will assess the correlation of the baseline biomarker and the subsequent response outcome and perform 2-sample t-tests comparing the mean baseline biomarker values between responders and non- responders.
Complete list of historical versions of study NCT01588613 on ClinicalTrials.gov Archive Site
  • Objective response, defined by CT scan measurements before and after treatment [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Change in tumor cell metabolic response measured by PET scan and correlation with tumor response by CT scan, PET, and direct tumor measurements [ Time Frame: From 4-6 days after beginning of treatment to end of treatment ] [ Designated as safety issue: No ]
  • Evaluate efficacy and utility of PET and CT scans in evaluating response to short-term treatment with erlotinib hydrochloride. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Evaluate efficacy and utility of PET and CT scans in evaluating response to short-term treatment with erlotinib hydrochloride by comparison of tumor response evaluation by PET scan with the same response evaluation performed by CT scan.
  • Correlate incidence of risk factors with relapse [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    Evaluate incidence of risk factors for relapse in the surgical pathology specimen obtained at time of surgical treatment, such as: positive margins, extracapsular invasion, vessels and perineural invasion. Compare with historical data from published trials of patients treated with surgery with curative intent as initial treatment.
  • Incidence of adverse effects or significant laboratory changes during the administration of erlotinib hydrochloride [ Time Frame: Up to day 14 ] [ Designated as safety issue: Yes ]
  • Any treatment-induced delay of the established date for definitive surgical treatment [ Time Frame: Day 15 ] [ Designated as safety issue: Yes ]
  • Objective response, defined by CT scan measurements before and after treatment [ Time Frame: Day before surgery ] [ Designated as safety issue: No ]
  • Change in tumor cell metabolic response measured by PET scan and correlation with tumor response by CT scan, PET, and direct tumor measurements [ Time Frame: From 4-6 days after beginning of treatment to end of treatment ] [ Designated as safety issue: No ]
  • Evaluate efficacy and utility of PET and CT scans in evaluating response to short-term treatment with erlotinib hydrochloride. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Evaluate efficacy and utility of PET and CT scans in evaluating response to short-term treatment with erlotinib hydrochloride by comparison of tumor response evaluation by PET scan with the same response evaluation performed by CT scan.
  • Correlate incidence of risk factors with relapse [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    Evaluate incidence of risk factors for relapse in the surgical pathology specimen obtained at time of surgical treatment, such as: positive margins, extracapsular invasion, vessels and perineural invasion. Compare with historical data from published trials of patients treated with surgery with curative intent as initial treatment.
  • Incidence of adverse effects or significant laboratory changes during the administration of erlotinib hydrochloride [ Time Frame: Up to day 14 ] [ Designated as safety issue: Yes ]
  • Any treatment-induced delay of the established date for definitive surgical treatment [ Time Frame: Day 15 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Erlotinib Hydrochloride and Surgery in Treating Patients With Head and Neck Cancer That Can Be Removed By Surgery
Pilot Study to Evaluate the Anti-tumor Effect of Erlotinib Administered Before Surgery in Operable Patients With Squamous Cell Carcinoma of the Head and Neck (HNSCC)

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Squamous Cell Carcinoma of the Skin
  • Stage I Squamous Cell Carcinoma of the Hypopharynx
  • Stage I Squamous Cell Carcinoma of the Larynx
  • Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage I Squamous Cell Carcinoma of the Oropharynx
  • Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage I Verrucous Carcinoma of the Larynx
  • Stage I Verrucous Carcinoma of the Oral Cavity
  • Stage II Squamous Cell Carcinoma of the Hypopharynx
  • Stage II Squamous Cell Carcinoma of the Larynx
  • Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage II Squamous Cell Carcinoma of the Oropharynx
  • Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage II Verrucous Carcinoma of the Oral Cavity
  • Drug: erlotinib hydrochloride
    erlotinib hydrochloride given PO
    Other Names:
    • CP-358,774
    • erlotinib
    • OSI-774
  • Procedure: therapeutic conventional surgery
    Undergo resection
  • Experimental: Group 1 (non-actively smoking patients)
    Patients receive low dose erlotinib hydrochloride PO QD for at least 14 days. At day 15 patients undergo surgical resection of the tumor.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Procedure: therapeutic conventional surgery
  • Experimental: Group 2 (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.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Procedure: therapeutic conventional surgery
Not Provided

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

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 date for surgery with a window of opportunity of at least 15 days
  • Patients with SCC tumors will be eligible for this protocol only if they have additional biopsy tissue already saved in our Tumor Tissue Core Laboratory for research purpose or if they agree to have additional biopsies of tumor with adjacent normal tissue available for molecular studies
  • Patients will only be eligible for this trial if they have tumor measurable on the CT scan 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 the upper limit of normal
  • Written informed consent must be obtained from all subjects prior to beginning therapy (subjects should have the ability to understand and be willing to sign a written informed consent document)

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 limit compliance with study requirements, significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction [within prior 3 months], uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction)
  • Subject with a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) 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 on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control; subjects who are women of childbearing potential and sexually active males must be willing to use effective contraception while on study
  • Human immunodeficiency virus (HIV)-positive subjects are excluded from the study
Both
18 Years and older
No
Not Provided
United States
 
NCT01588613
CCCWFU 60307, NCI-2009-01255
Not Provided
Comprehensive Cancer Center of Wake Forest University
Comprehensive Cancer Center of Wake Forest University
National Cancer Institute (NCI)
Principal Investigator: Mercedes Porosnicu Comprehensive Cancer Center of Wake Forest University
Comprehensive Cancer Center of Wake Forest University
July 2013

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