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

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.

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

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy, radiotherapy, or investigational antitumor drug

- No other concurrent investigational agents