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 paclitaxel and carboplatin, 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 a monoclonal antibody with chemotherapy and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients who are undergoing surgery for stage III or stage IV head and neck cancer.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer Laryngeal Cancer lip and oral cavity cancer Oropharyngeal Cancer paranasal sinus and nasal cavity cancer Salivary Gland Cancer	Drug: carboplatin  Drug: cetuximab  Drug: paclitaxel  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: monoclonal antibody therapy  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the effect of induction therapy comprising cetuximab, paclitaxel, and carboplatin followed by chemoradiotherapy comprising cetuximab, paclitaxel, carboplatin, and radiotherapy on 1-year event-free survival (freedom from surgery at the primary site and freedom from recurrence and death) in patients with stage III or IV operable squamous cell cancer of the head and neck.

Secondary

• Determine the pathologic antitumor response at the primary site in patients treated with this regimen.
• Determine disease-free and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine local/regional and distant failure rates in patients treated with this regimen.
• Determine the effect of this treatment regimen on selective biologic pathways, total and phosphorylated epidermal growth factor receptor, ERK/MAPK, and P13K/AKT in these patients.

OUTLINE: This is a multicenter study.

• Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. During week 7 or 8, patients undergo biopsy and evaluation of the primary site. Patients then proceed to chemoradiotherapy.
• Chemoradiotherapy (weeks 9-13): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 15 minutes on days 57, 64, 71, 78, and 85. Patients also undergo radiotherapy once daily, 5 days a week, on weeks 9-13. Patients with a negative biopsy at week 7 or 8 and who achieve a complete clinical and pathological response at the primary site after induction therapy receive additional chemoradiotherapy beginning at week 14. Patients receive cetuximab, carboplatin, and paclitaxel as in chemoradiotherapy (as outlined above) on days 92, 99, and 106 (weeks 14-16). Patients also undergo radiotherapy once daily, 5 days a week, on weeks 15 and 16. Patients with N1-N3 disease undergo neck dissection on weeks 20-21.

Patients with a positive biopsy at week 7 or 8 or persistent tumor at the primary site after induction therapy undergo a second biopsy on week 14. Patients with a negative biopsy at week 14 receive additional chemoradiotherapy (as outlined above) on weeks 14-16. Patients with N1-N3 disease undergo neck dissection on weeks 20-21. Patients with a positive biopsy at week 14 do not receive additional chemoradiotherapy, but rather undergo surgical resection of the primary site on weeks 18-19. Patients with N1-N3 disease also undergo neck dissection at this time.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study within 2.2 years.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell cancer of the head and neck
• Biopsy confirmed at the primary site
• Stage III or IV (T2-4, N1-N3)
• No nasopharyngeal cancer
• Potentially operable with a high likelihood of achieving R0 resection
• No fixed nodal metastasis to the spine or carotid artery
• No invasion of the root of the tongue, pharyngeal muscle, post pharynx, or vertebral fascia
• No invasion of laryngeal cartilage into strap muscles or tracheal invasion > 1 cm
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
• Patients with clinically palpable cervical lymph nodes must be evaluated by CT scan and confirmed with fine needle aspiration
• Patients with non-palpable neck nodes must be evaluated by CT scan
• Radiographic findings are acceptable in the absence of clinically palpable lymph nodes

PATIENT CHARACTERISTICS: Age

• 18 to 80

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No uncontrolled arrhythmias

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known allergy to murine proteins or Cremophor EL
• No other malignancy within the past 5 years except lobular carcinoma in situ of the breast, carcinoma in situ of the cervix, basal cell cancer, or excised and controlled cutaneous squamous cell cancer (< 200 mm thick)

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for head and neck cancer
• No prior chimerized or murine monoclonal antibody therapy
• No prior anti-epidermal growth factor receptor (EGFR) antibody therapy

Chemotherapy

• No prior chemotherapy for head and neck cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for head and neck cancer
• No concurrent cobolt-60

Surgery

• No prior surgery for head and neck cancer

Other

• No prior tyrosine kinase inhibitor therapy, including inhibitors targeting EGFR pathways

Rhode Island
      Roger Williams Medical Center, Providence,  Rhode Island,  02908-4735,  United States; Recruiting

Study chairs or principal investigators

Harold J. Wanebo, MD,  Study Chair,  Roger Williams Medical Center   
Barbara A. Burtness, MD,  Yale Cancer Center   

Study ID Numbers:  CDR0000378194; ECOG-E2303; NCT00089297
Record last reviewed:  January 2005
Last Updated:  January 18, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089297
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08