RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin, 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. Cetuximab may make the tumor cells more sensitive to radiation therapy and chemotherapy. Giving monoclonal antibody therapy together with chemoradiotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together with radiation therapy works in treating patients with locally advanced or regional stage IV head and neck cancer that cannot be removed by surgery.

Condition	Treatment or Intervention	Phase
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 oropharynx	Drug: cetuximab  Drug: cisplatin  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine 2-year progression-free survival in patients with unresectable locally advanced or regional stage IV squamous cell or undifferentiated carcinoma of the head and neck treated with cetuximab, cisplatin, and definitive radiotherapy.

Secondary

• Determine local response rate and overall survival in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Correlate epidermal growth factor receptor (EGFR) expression by immunohistochemistry, EGFR phosphorylation, map kinase, AKT, STAT3, and other tissue and serum tests with toxicity of this regimen and outcomes in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor site (hypopharynx vs oropharynx vs oral cavity vs larynx), primary tumor stage (T1-3 vs T4), and nodal status (N0 vs N1 vs N2-3).

• Cetuximab therapy: Patients receive an initial loading dose of cetuximab IV over 2 hours on day 1. Patients then receive cetuximab IV over 1 hour on days 8, 15, 22, 29, 36, 43, 50, and 57.
• Chemoradiotherapy: Beginning on day 15 of cetuximab therapy, patients undergo radiotherapy once daily, 5 days a week, for at least 7 weeks. Patients also receive cisplatin IV over 1-2 hours on days 15, 36, and 57.
• Cetuximab maintenance therapy: After the completion of chemoradiotherapy, patients continue to receive cetuximab IV over 1 hour once weekly for 6-12 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 10 years.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study within 19.5 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell or undifferentiated carcinoma of the head and neck (excluding nasopharynx, paranasal sinus, and parotid gland)
• Locally advanced or regional stage IV disease
• No evidence of distant metastases
• No disease metastases below the clavicles or elsewhere (M_1)
• Must have demonstrable primary tumor site
• Unresectable disease
• Meets the following criteria for unresectable disease by tumor site:
• Hypopharynx, meeting 1 of the following criteria:
• Extension across the midline of the posterior pharyngeal wall
• Any evidence of fixation to the cervical spine
• Larynx
• Direct subglottic extension (> 3 cm) into surrounding muscle or skin
• Oral cavity
• Lesion precluding functional reconstruction
• Base of tongue, meeting 1 of the following criteria:
• Extension into the root of the tongue
• Patient refuses total glossectomy
• Tonsillar area, meeting 1 of the following criteria:
• Extension into pterygoid area as manifested by x-ray or trismus
• Extension across midline of pharyngeal wall
• Direct extension into soft tissue of the neck
• Unilateral neck node metastases fixed to carotid artery, mastoid, base of skull, or cervical spine with any of the above tumors
• Patients who refuse surgery but whose tumors are technically resectable OR whose tumors are unresectable for medical reasons are not eligible
• Patients requiring total glossectomy are eligible
• Measurable disease
• No postoperative recurrence
• No prior head and neck or lung cancer

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Alkaline phosphatase ≤ 3 times normal
• AST or ALT ≤ 3 times normal
• Bilirubin ≤ 1.5 mg/dL
• No clinically apparent jaundice

Renal

• Creatinine ≤ 1.2 mg/dL OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No myocardial infarction within the past 3 months
• No uncontrolled congestive heart failure
• No unstable or uncontrolled angina

Pulmonary

• No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to tolerate fluid load
• No active systemic infection
• No known allergy to murine proteins
• No other malignancy within the past 3 years except resected basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ tumors

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior chimerized or murine monoclonal antibody

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the head and neck region

Surgery

• At least 14 days since major surgery, including dental extraction
• No prior excisional surgery of head and neck tumor

Other

• No prior drugs that target the epidermal growth factor receptor pathway

Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States; Recruiting

Study chairs or principal investigators

Corey Jay Langer, MD,  Study Chair,  Fox Chase Cancer Center   
William A. Flood, MD,  Milton S. Hershey Medical Center   

Study ID Numbers:  CDR0000390923; ECOG-E3303; NCT00096174
Record last reviewed:  January 2005
Last Updated:  February 24, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096174
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08