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 use 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. Combining chemotherapy with monoclonal antibody therapy and radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining cetuximab, cisplatin, and radiation therapy in treating patients who have advanced stage III or stage IV head and neck cancer.

Condition	Treatment or Intervention	Phase
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity stage IV squamous cell carcinoma of the lip and oral cavity recurrent squamous cell carcinoma of the oropharynx recurrent squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity stage IV squamous cell carcinoma of the hypopharynx Quality of Life	Drug: cetuximab  Drug: cisplatin	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the response rate in patients with newly diagnosed or recurrent, advanced stage III or IV squamous cell carcinoma of the head and neck treated with 6 infusions of cetuximab at loading/maintenance doses in combination with 2 infusions of cisplatin concurrent with standard/delayed accelerated hyperfractionated radiotherapy followed by 4 weeks of single agent cetuximab. II. Assess the safety profile of this treatment regimen in this patient population. III. Evaluate time to disease progression and survival in these patients treated with this regimen. IV. Assess the impact of this treatment regimen on the quality of life of these patients.

PROTOCOL OUTLINE: Patients receive a loading dose of cetuximab IV over 120 minutes on week 1 followed by 5 weekly maintenance doses over 60 minutes on weeks 2-6. Patients receive cisplatin IV over 30 minutes on weeks 1 and 4 beginning 1 hour after completion of cetuximab infusion. Radiotherapy is administered once daily during weeks 1-4 and twice daily during weeks 5 and 6. Following the initial 6 weeks of treatment, patients receive additional cetuximab IV over 30 minutes weekly on weeks 7-10. Quality of life is assessed at baseline, within 4 weeks after completion of all treatment, and at 3-4 months. Patients are followed at 4-6 weeks, 12-16 weeks, every 3 months for 2 years, every 4 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Newly diagnosed or recurrent, advanced stage III or IV squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or paranasal sinus/nasal cavity; M0; No nasopharyngeal cancer
• Measurable or evaluable disease

--Prior/Concurrent Therapy--

• Biologic therapy: No prior murine monoclonal antibody therapy; No prior cetuximab; No prior immunotherapy
• Chemotherapy: At least 3 years since prior chemotherapy; No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to the head or neck region; No other concurrent radiotherapy
• Surgery: At least 60 days since prior surgery; Diagnostic biopsy allowed

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%; ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,000/mm3; Granulocyte count at least 1,500/mm3; Hemoglobin at least 9 g/dL; Platelet count at least 100,000/mm3 Hepatic: Alkaline phosphatase no greater than 2.5 times upper limit of normal; (ULN) AST no greater than 2.5 times ULN; Bilirubin no greater than 1.5 times ULN
• Renal: Creatinine no greater than 1 times ULN; Creatinine clearance at least 60 mL/min; Calcium no greater than 11.5 mg/dL
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Michael J. Zelefsky,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000067817; MSKCC-99095; NCI-G00-1785
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005814
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08