Erlotinib in Treating Patients With Metastatic and/or Recurrent Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with recurrent and/or metastatic head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Determine the relationship between response rate and number of CA repeats in intron 1 of the epidermal growth factor receptor (EGFR) in patients with metastatic and/or locally recurrent squamous cell carcinoma of the head and neck (SCCHN) treated with the EGFR inhibitor erlotinib hydrochloride. Secondary Determine the relationship between the number of CA repeats in intron 1 of the EGFR gene and time to disease progression and survival in patients treated with this drug. Determine cutaneous and other toxicities of erlotinib hydrochloride in patients with different numbers of CA repeats in intron 1 of the EGFR gene. Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples in patients with different numbers of CA repeats in intron 1 of the EGFR genes treated with this drug. Determine the relationship between erlotinib hydrochloride exposure (utilizing total and unbound erlotinib hydrochloride concentrations) and outcome, toxicity, and pharmacodynamic effects (upregulation of p27) in patients with different numbers of CA repeats. OUTLINE: This is a multicenter study. Patients are stratified according to genotype of intron 1 of the epidermal growth factor receptor (16/16 vs 16/20 or 20/20). Patients receive oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Official Title
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Genotypic-Based Pharmacodynamic Evaluation of Erlotinib (Erlotinib (Tarceva™, OSI Pharmaceuticals, Uniondale, NY) in Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck Metastatic and/or locally recurrent disease No undifferentiated and nonkeratinizing carcinomas, including lymphoepitheliomas of all locations, as well as tumors of the parotid gland WHO Type I squamous cell carcinoma of the nasopharynx are allowed Incurable with surgery or radiotherapy Measurable disease, defined as ≥ 1 target lesion ≥ 20 mm OR ≥ 10 mm on spiral CT scan If the only site of measurable disease is in a previously irradiated area, the patient must have documented progressive disease by tomography or biopsy-proven residual carcinoma No symptomatic brain metastases that are not stable, are not adequately controlled with fixed-dose oral steroids, are potentially life-threatening, or have required radiotherapy within the last 14 days PATIENT CHARACTERISTICS: ECOG performance status 0-2 Predicted life expectancy ≥ 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and/or ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must practice effective contraceptive measures No other prior malignancy within the past 3 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer No active or uncontrolled infection or other serious illnesses or medical conditions No history of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than two prior chemotherapy regimens for locally recurrent and/or metastatic disease Prior induction chemotherapy or chemoradiotherapy with curative intent for local disease allowed provided patient has received no more than two prior chemotherapy regimens for recurrent disease Prior therapy must have been completed a minimum of 14 days prior to study AND patient has recovered No prior molecular-directed therapies, such as tyrosine kinase inhibitors and/or monoclonal antibodies At least 14 days must have elapsed between the end of radiotherapy and study registration and recovered At least 14 days since prior surgery AND wound healing has occurred At least 7 days since prior herbal extracts and tinctures with CYP3A inhibitory activity, including any of the following: Hydrastis canadensis (goldenseal) Uncaria tomentosa (cat's claw) Echinacea angustifolia roots Trifolium pratense (wild cherry) Matricaria chamomilla (chamomile) Glycyrrhiza glabra (licorice) Dillapiol Naringenin No other concurrent anticancer therapy or other investigational agents No concurrent administration of any of the following: Phenytoin Carbamazepine Rifampicin Barbiturates Hypericum perforatum (St. John's wort) CYP3A inhibitors (e.g., itraconazole)

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
Allocation: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: erlotinib hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between response rate and number of CA repeats in intron 1 of the EGFR |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  |  | 
| Survival |  |  | 
| Toxicity |  |  | 
| Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples |  |  | 
| Relationship between erlotinib hydrochloride exposure and outcome, toxicity, and pharmacodynamic effects |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent metastatic squamous neck cancer with occult primary, metastatic squamous neck cancer with occult primary squamous cell carcinoma