Adjuvant Erlotinib After Completing Chemoradiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving erlotinib after chemoradiotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of adjuvant erlotinib when given after completing chemoradiotherapy in treating patients with locally advanced squamous cell carcinoma (cancer) of the head and neck.

Detailed Description
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OBJECTIVES: Primary Determine the recommended dose of adjuvant erlotinib after the completion of chemoradiotherapy in patients with stage III, IVA, or IVB squamous cell carcinoma of the head and neck. Determine the toxicity of this drug in these patients. Determine the effects of this drug on plasma and urinary angiogenic factors (specifically vascular endothelial growth factor receptor [VEGFR], VEGFR1, VEGFR2, and basic fibroblast growth factor levels) in these patients. Compare the disease-free survival of patients treated with this drug after chemoradiotherapy vs historical control patients treated with chemoradiotherapy alone. Correlate levels of angiogenic factors with initial blood vessel concentration in the tumor and the presence or absence of EGFRvIII mutation in patients treated with this drug. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive oral erlotinib once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 8 patients are treated at that dose level. Patients are followed at 4 weeks, every 12 weeks for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study.

Official Title
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A Phase I Study of Adjuvant OSI-774 (Tarceva®) in Patients Following Combined Chemo-Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck Stage III, IVA, or IVB Must have completed cisplatin- or carboplatin-based chemoradiotherapy within the past 4-12 weeks Prior radiotherapy must have been given with a radical intent with receipt of at least 90% of planned dose No evidence of disease or presence of inoperable minimal residual disease, defined by 1 of the following: Complete response at primary tumor site and nodes (with or without nodal surgery after chemoradiotherapy) Negative lymph node status (by physical or radiological exam) AND persistent tumefaction less than 25% of original tumor size or residual mass due to scarring Tumor tissue samples available for EGFRvIII mutation analysis No known brain metastasis PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic ALT/AST < 2 times upper limit of normal (ULN) Bilirubin < ULN (unless due to Gilbert's syndrome) Renal Creatinine < 1.5 times ULN Cardiovascular No myocardial infarction within the past year No cardiac ventricular arrhythmias requiring medication No history of cardiac disease No uncontrolled high blood pressure No unstable angina No congestive heart failure Ophthalmic No history of severe dry eye syndrome, Sjögren's syndrome, or keratoconjunctivitis sicca No severe exposure keratopathy No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) No abnormal corneal sensitivity test (Schirmer test or similar tear production test) No disorder that might increase the risk for epithelium-related complication (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis) No congenital abnormality (e.g., Fuch's dystrophy) No ocular inflammation or infection Gastrointestinal Able to take oral medication No gastrointestinal (GI) tract disease requiring IV alimentation No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis) No active peptic ulcer disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious active infection No other serious underlying medical condition that would preclude study participation No prior allergic reaction to compounds of similar chemical or biological composition to erlotinib No other malignancy with the past 5 years except adequately treated non-melanoma skin cancer (unless in the same area treated with radical radiotherapy) or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Recovered from prior chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics Recovered from prior radiotherapy Surgery See Disease Characteristics No prior surgical procedure affecting absorption No concurrent ophthalmic surgery Other More than 4 weeks since other prior investigational drugs No other concurrent investigational agents No other concurrent anticancer therapy Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance with respect to INR Concurrent nasogastric or gastrostomy tube feeding for dysphagia allowed provided there is no evidence of significant residual mucositis (i.e., > grade 1)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: erlotinib hydrochloride|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity/feasibility assessed by NCI CTC v2.0 at the end of course 1 |  |  | 
| Recommended phase II dose at the end of course 1 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlative studies (archival and prospective) at accrual completion |  |  | 
| Disease-free survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer