Gefitinib, Paclitaxel, and Radiation Therapy in Treating Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving gefitinib and paclitaxel together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gefitinib and paclitaxel when given together with radiation therapy in treating patients with advanced or recurrent squamous cell carcinoma (cancer) of the head and neck.

Detailed Description
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OBJECTIVES: Primary Determine the dose-limiting toxicity, toxicity profile, and maximum tolerated dose (MTD) of gefitinib and paclitaxel administered with radiotherapy in patients with advanced or recurrent squamous cell carcinoma of the head and neck. Secondary Determine the efficacy of this regimen in patients treated at the MTD. OUTLINE: This is a pilot, dose-escalation study of gefitinib and paclitaxel. Patients receive oral gefitinib once daily beginning on day 1 and continuing until completion of radiotherapy. Patients receive paclitaxel IV over 1 hour on days 8, 15, 22, 29, 36, and 43 and undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, 50-54, and 57-61. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A cohort of 6 additional patients receive treatment at the MTD. Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months for 3 years. PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 2 years.

Official Title
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A Pilot Phase I Dose Escalation Study Of The EGFR Tyrosine Kinase Inhibitor Gefitinib (Iressa) Combined With Paclitaxel (Taxol) And External Beam Radiation Therapy In Patients With Advanced 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: gefitinib
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed squamous cell (epidermoid) carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or maxillary sinus Stage III or IV disease Distant metastases allowed provided both of the following are true: Metastases are confined to the head and neck region Metastases are encompassable in a radiotherapy field with curative intent Locally recurrent disease after primary surgery allowed Meets 1 of the following criteria: Unresectable disease Patient prefers chemoradiotherapy over surgery Measurable disease No brain metastases and/or carcinomatous meningitis PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Hemoglobin > 10 g/dL Platelet count > 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Hepatic Bilirubin < 2.0 times upper limit of normal (ULN) AST/ALT ≤ 2.5 times ULN Renal Creatinine < 1.5 times ULN OR Creatinine clearance ≥ 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Pulmonary No clinically active interstitial lung disease Chronic, stable, asymptomatic radiographic changes allowed Other No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs or Cremophor^® EL No AIDS or primary immunodeficiencies No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix Probability of recurrence of the prior malignancy < 5% No other concurrent uncontrolled illness No ongoing or active serious infection No psychiatric illness or situation that would preclude study compliance or giving informed consent Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for cancer No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior therapeutic radiotherapy to the head and neck region No prior radiotherapy for cancer Surgery See Disease Characteristics At least 4 weeks since prior major surgery and recovered Other No prior gefitinib or other epidermal growth factor receptor inhibitors More than 4 weeks since prior non-approved or investigational agents No concurrent administration of any of the following: Phenytoin Carbamazepine Barbiturates Rifampin Hypericum perforatum (St. John's wort) Oxcarbazepine Rifapentine Amifostine Modafinil Other CYP3A4 enzyme inducers Other anticancer agents or investigational drugs Combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gefitinib|nan|
|Drug: paclitaxel|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular targets analysis of epidermal growth factor receptor (EGFR) downstream signaling pathway as assessed by tissue biopsies and serum cytokines at baseline, days 8 and 29, and 12 weeks after completion of study treatment |  |  | 
| Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years |  |  | 

 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 lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx