RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with docetaxel may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with docetaxel and radiation therapy in treating patients who have locally advanced head and neck cancer.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer Laryngeal Cancer lip and oral cavity cancer Nasopharyngeal Cancer Oropharyngeal Cancer	Drug: docetaxel  Drug: erlotinib  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib when administered with docetaxel and radiotherapy in patients with locally advanced squamous cell cancer of the head and neck.
• Determine the toxicity of this regimen in these patients.
• Determine the pharmacokinetic profile of erlotinib alone and in combination with docetaxel in these patients.
• Determine the overall and complete response rate in patients treated with this regimen.
• Determine the overall, disease-free, and progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of erlotinib and docetaxel.

Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.

Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel 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.

Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24 weeks for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 3-24 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
• Stage III or IV (locally advanced disease)
• No distant metastatic disease
• Measurable disease
• No salivary gland or paranasal sinus squamous cell carcinoma
• No known brain metastases or direct cerebral invasion by tumor
• Intracranial extension without cerebral involvement may be allowed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin normal
• AST/ALT no greater than 2 times upper limit of normal
• Prothrombin time normal

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No clinically significant heart disease
• No New York Heart Association class III or IV heart disease
• No significant arrhythmias requiring medication
• No symptomatic coronary artery disease
• No myocardial infarction within the past 6 months
• No second- or third-degree heart block or bundle branch block
• No symptomatic congestive heart failure
• No unstable angina pectoris

Other

• No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or docetaxel, including other drugs formulated with polysorbate 80
• No pre-existing peripheral neuropathy grade 2 or greater
• No other concurrent uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
• No patients who are considered poorly compliant
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent routine colony-stimulating factors

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No prior investigational antitumor drugs
• No other concurrent commercial or investigational anticancer agents or therapies

Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting

Study chairs or principal investigators

Scot C. Remick, MD,  Study Chair,  Ireland Cancer Center   

Study ID Numbers:  CDR0000258046; CWRU-1301; NCI-5389; CWRU-050212; NCT00049283
Record last reviewed:  May 2004
Last Updated:  April 4, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049283
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08