Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00720304

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with docetaxel and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well erlotinib given together with docetaxel and radiation therapy works in treating patients with stage III or stage IV squamous cell carcinoma of the head and neck.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: docetaxel Drug: erlotinib hydrochloride Genetic: fluorescence in situ hybridization Genetic: polymerase chain reaction Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Procedure: therapeutic conventional surgery Radiation: intensity-modulated radiation therapy Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the time to progression in patients with locally advanced squamous cell carcinoma of the head and neck treated with erlotinib hydrochloride in combination with docetaxel and radiotherapy.

Secondary

Determine objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival in patients treated with this regimen.
Determine the toxicities of this regimen in these patients.
Determine the dose and effect of this treatment on biologic correlates in tumor tissue and/or surrounding mucosa.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Beginning on week 3, patients receive docetaxel IV over 1 hour once a week and radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery. Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.

Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.

After completion of study therapy, patients will be evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: oral erlotinib hydrochloride	Drug: docetaxel Beginning on week 3, patients receive docetaxel IV over 1 hour once a week Drug: erlotinib hydrochloride oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity Genetic: fluorescence in situ hybridization Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Genetic: polymerase chain reaction Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Other: immunoenzyme technique Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Other: immunohistochemistry staining method Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Other: laboratory biomarker analysis Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Other: pharmacological study Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. Procedure: therapeutic conventional surgery At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery.Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy. Radiation: intensity-modulated radiation therapy radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity. Radiation: radiation therapy radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

Arm

Intervention/Treatment

Experimental: oral erlotinib hydrochloride

Drug: docetaxel

Beginning on week 3, patients receive docetaxel IV over 1 hour once a week

Drug: erlotinib hydrochloride

oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity

Genetic: fluorescence in situ hybridization

Genetic: polymerase chain reaction

Other: immunoenzyme technique

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Other: pharmacological study

Procedure: therapeutic conventional surgery

At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery.Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.

Radiation: intensity-modulated radiation therapy

radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

Radiation: radiation therapy

radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

Progression-free-survival [3 yrs after treatment]
Time to progression [3 yrs after treatment]

Secondary Outcome Measures

Response rate (complete response, partial response, stable disease, and disease progression) [3 yrs after treatment]
Overall survival [evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.]
Toxicities [evaluated every 2 weeks]
Predictive values of EGFR/TGF-α, VEGF [collection at baseline and periodically during study.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck
Stage III or IV disease
No distant metastatic disease
Measurable disease (according to RECIST)
No salivary gland and paranasal sinus squamous cell carcinoma
No known brain metastases or direct cerebral invasion by tumor
Intracranial extension (without cerebral involvement) may be allowed

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 12 weeks
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥10 g/dL
Total bilirubin normal
Alkaline phosphatase AND AST and ALT meeting the following criteria:
Alkaline phosphatase normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN AND AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 5 times ULN AND AST and ALT normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
No clinically significant heart disease including any of the following:
NYHA class III or IV heart disease
Significant arrhythmias requiring medication
Symptomatic coronary artery disease
Myocardial infarction within the previous six months
Second- or third-degree heart block or bundle-branch block
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80
No pre-existing peripheral neuropathy ≥ grade 2
No uncontrolled concurrent illness including, but not limited to, any of the following:
Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would preclude compliance with study requirements
No HIV positivity
No other prior malignancy except for any of the following:
Squamous cell or basal cell carcinoma of the skin
Carcinoma in situ of the cervix
Cancer that was treated more than 5 years ago and the patient has remained disease-free
Not poorly compliant