• Disease-free survival (DFS) [ Designated as safety issue: No ]
  

• Overall survival (OS) [ Designated as safety issue: No ]
  
• Local-regional control (LRC) [ Designated as safety issue: No ]
  
• Mucositis toxicity ≥ grade 3 [ Designated as safety issue: Yes ]
  
• Other toxicity ≥ grade 3 [ Designated as safety issue: Yes ]
  
• Protocol treatment delivery [ Designated as safety issue: No ]
  
• Death during or within 30 days of discontinuation of protocol treatment [ Designated as safety issue: No ]
  
• Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D) [ Designated as safety issue: No ]
  
• Quality of life as measured by Functional Assessment of Cancer Therapy-General version [ Designated as safety issue: No ]
  
• Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC [ Designated as safety issue: No ]
  
• Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC [ Designated as safety issue: No ]
  
• Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve disease-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.

Secondary

• Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.
• Correlate the expression of EGFR and its down-stream molecules with outcome in patients participating in this component of the trial.
• Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
• Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
• Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I.

In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment.

NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.

Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven (from primary lesion and/or lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx

  • Stage III or IV disease (T2, N2-3, M0; T3-4, any N, M0)

    • No distant metastases

  • The following primary tumor sites are excluded:

    • Oral cavity
    • Nasopharynx
    • Sinuses
    • Salivary glands

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,800/mm^3
• Platelets ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
• Bilirubin ≤ 1.5 mg/dL (Gilbert's disease as the sole cause of elevated bilirubin may be allowed at the discretion of the principal investigator)
• AST or ALT ≤ 2 times the upper limit of normal
• Serum creatinine ≤ 1.5 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
• No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• No unstable angina and/or congestive heart failure requiring hospitalization in past 6 months
• Left ventricular ejection fraction ≥ 45%
• No transmural myocardial infarction within the last 6 months
• No acute bacterial or fungal infection requiring intravenous antibiotics
• No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy

• No acquired immune deficiency syndrome (AIDS)

  • HIV testing is not required for entry into this protocol
  • Protocol-specific requirements may also exclude immuno-compromised patients
• No prior allergic reaction to the study drug(s)
• No other uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
• No comorbidity of uncontrolled diabetes (i.e., symptomatic hyperglycemia)
• No other severe active comorbidity

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy for the study cancer

  • Prior chemotherapy for a different cancer is allowed
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
• No radical or modified neck dissection
• No prior therapy that specifically and directly targets the EGFR pathway
• Patients participating in RTOG-0522 are also eligible for and are strongly encouraged to participate in RTOG-0514, the Head and Neck tissue banking protocol