RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if radiation therapy is more effective with or without cetuximab for cancer of the oropharynx, hypopharynx, or larynx.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without cetuximab in treating patients who have stage III or stage IV cancer of the oropharynx, hypopharynx, or larynx.

Condition	Treatment or Intervention	Phase
Oral Cancer Throat Cancer	Drug: cetuximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: monoclonal antibody therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the rate of locoregional disease control maintained for 1 year in patients with advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx treated with radiotherapy with or without concurrent cetuximab.
• Compare the response rates, progression-free survival and overall survival rates, and quality of life in patients treated with these regimens.
• Compare acute and late toxicity of these regimens in these patients.
• Determine tumor epidermal growth factor receptor levels in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by Karnofsky performance status (60-80% vs 90-100%), nodal stage (N0 vs N+), tumor stage (T1-3 vs T4), and radiotherapy schedule (concurrent boost vs once daily vs twice daily).

Patients are randomized to 1 of 2 treatment arms:

• Patients undergo radiotherapy beginning on day 1. Patients are assigned to 1 of 3 radiotherapy groups:
• Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days a week for 2.5 weeks.
• Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks.
• Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks.
• Arm II: Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats every week for 7 courses. Beginning on day 8, patients undergo radiotherapy as in arm I concurrently with maintenance cetuximab. There must be an hour interval between the completion of cetuximab infusion and the start of any radiotherapy. Patients with more than N1 neck disease at initial presentation undergo neck dissection 4-8 weeks after the completion of radiotherapy.

Quality of life is assessed before initiation of study therapy, at 8 weeks, and then every 4 months for 1 year.

Patients are followed at 8 weeks, every 4 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 416 patients (208 per arm) will be accrued for this study within approximately 5 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
• Stage III OR
• Stage IV without distant metastases
• Measurable disease
• Tumor tissue available for immunohistochemical assay of epidermal growth factor receptor expression

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 1 year

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 50 mL/min
• Calcium normal

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Medically able to withstand a course of definitive radiotherapy
• No medical or psychologic condition that would preclude informed consent or compliance
• No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior cetuximab or other murine monoclonal antibody

Chemotherapy:

• At least 3 years since prior systemic chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to head and neck
• No other concurrent radiotherapy

Surgery:

• No prior surgery for indicator lesion except biopsy
• Study radiotherapy must not be a part of a postoperative regimen after primary surgical resection

New Jersey
      ImClone Systems, Incorporated, Somerville,  New Jersey,  08876,  United States
      Kimball Medical Center, Lakewood,  New Jersey,  08701,  United States
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States

Study chairs or principal investigators

James A. Bonner, MD,  Study Chair,  UAB Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067468; UAB-9901; IMCL-CP02-9815; NCI-G99-1657
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004227
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08