Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

A Phase II Study of Erlotinib and Radiation Therapy in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck

RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride may also make tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x- rays and other types of radiation to kill tumor cells. Giving erlotinib hydrochloride together with radiation therapy may be an effective treatment for patients with head and neck cancer.PURPOSE: This phase II trial is studying how well giving erlotinib hydrochloride together with radiation therapy works in treating patients with stage III-IV squamous cell cancer of the head and neck.

PRIMARY OBJECTIVES:I. To determine the time to progression of the combination of the EGFR inhibitor erlotinib and radiation therapy. SECONDARY OBJECTIVES:I. To determine objective response rate, locoregional control rate, duration of response, patterns of failure, overall survival, toxicities and quality of life outcomes of the combination of erlotinib and concurrent radiation therapy.II. To determine the pharmacokinetic profile of erlotinib. Additional analyses of the pharmacokinetic data on patients receiving daily erlotinib treatment via their feeding tube will be conducted. III. To determine the effect of treatment and dose of treatment on biologic correlates in tumor tissue and/or surrounding mucosa, EGFR expression and phosphorylation status, serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF, fluorescence in situ hybridization (FISH) for ERBB2 for gene amplification, DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy material for mutation screening, gene expression profiling on pre-treatment biopsy material to identify predictors of response to treatment, apoptosis (TUNEL assay), Ki67 (nuclear proliferation antigen)IV. To determine the utility of the comprehensive geriatric assessment, in predicting tolerance to treatment in patients >= 65 years included in this trial. OUTLINE: Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up at 6 months, every 3 months for 2 years, and then every 6 months for 2 years.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease, who are not candidates or have declined definitive surgical resection or for administration of standard chemotherapy during radiation therapy because of any of the following reasons: advanced age (>= 70 years); poor ECOG performance status (2 or 3); significant comorbidities, as reflected by a Charlson comorbidity index score of >= 3; abnormal hematopoietic, hepatic or renal function; patient's decision after applicable standard treatment options have been offered and declined by patient
• No prior chemotherapy, radiation therapy, or investigational antitumor drug
• Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria
• Life expectancy of greater than 12 weeks
• Patients must have normal hepatic function or well compensated liver disease as defined by the Child-Pugh classification of severity of liver disease; patients with hepatic impairment (total bilirubin greater than upper limit of normal [ULN] or well-compensated disease [Child-Pugh class A] enrolled in the trial will be closely monitored, especially those with total bilirubin > 3 times ULN; dosage modifications (therapy interruption or discontinuation) may be necessary for severe changes in liver function; patient management will follow the FDA-approved labeling recommendations
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• All histologies other than squamous cell carcinoma
• Salivary gland paranasal sinus and nasopharyngeal squamous cell carcinoma
• Patients who have had prior chemotherapy or radiotherapy
• Patients with metastatic disease
• Patients with ECOG performance status of 4
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ERLOTINIB
• Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient is currently disease-free from the previous cancer
• Patients may not be receiving any other investigational agent
• Pregnant women; breastfeeding should be discontinued