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.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer Laryngeal Cancer lip and oral cavity cancer Nasopharyngeal Cancer Oropharyngeal Cancer paranasal sinus and nasal cavity cancer	Drug: gefitinib  Drug: paclitaxel  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase I

Further Study Details: 

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 on days 1-112 and paclitaxel IV over 1 hour on days 8, 15, 22, 29, 36, and 43. In addition, patients 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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
• 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

District of Columbia
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
Maryland
      National Naval Medical Center, Bethesda,  Maryland,  20889-5000,  United States; Recruiting
      NCI - Metabolism Branch;MET, Bethesda,  Maryland,  20892-1374,  United States; Recruiting
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting

Study chairs or principal investigators

Carter Van Waes, MD, PhD,  Study Chair,  NIDCD - Head and Neck Surgery Branch   

Study ID Numbers:  CDR0000362055; NCI-04-C-0141; NCI-5926; NCT00083057
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00083057
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08