Induction Chemotherapy Followed By Cetuximab and Radiation in HPV-Associated Resectable Stage III/IV Oropharynx Cancer

Inclusion Criteria:

   - Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as
   determined by Hematoxylin and eosin (H&E) staining

      - Newly diagnosed disease

      - Resectable disease OR disease that is expected to become resectable after study
      treatment

      - Stage III, IVA, or IVB disease as determined by imaging studies (computed
      tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI)
      required) and a complete head and neck exam

   - Paraffin-embedded tumor specimen available for central confirmation of HPV-associated
   disease as determined by H&E staining and in-situ hybridization (ISH) for HPV-16 and
   immunohistochemistry (IHC) for p16

      - HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive

      - Non-HPV-associated disease is defined as p16 IHC-negative

      - NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16
      ISH

   - Measurable disease of the primary tumor or nodes by clinical and radiographic methods,
   defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by
   radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one
   dimension if the radiographic exam utilizes spiral CT scan)

   - No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or
   cervical spine

   - No evidence of distant metastases

   - Eastern Cooperative Oncology Group performance status 0-1

   - Granulocytes ≥ 1,000/mm^3

   - Platelet count ≥ 100,000/mm^3

   - Total serum bilirubin ≤ 1.5 mg/dL

   - Creatinine clearance ≥ 60 mL/min

   - Negative pregnancy test

   - Fertile patients must use effective contraception

   - No history of another malignancy (except for carcinoma in situ of the cervix and/or
   nonmelanomatous skin cancer) unless it has been curatively treated and the patient has
   been disease-free for ≥ 2 years

   - Patients with any of the following within the past 6 months are eligible provided they
   have been evaluated by a cardiologist and/or neurologist before study entry:

      - New York Heart Association (NYHA) class III-IV congestive heart failure

      - Cerebrovascular accident or transient ischemic attack

      - Unstable angina

      - Myocardial infarction (with or without ST elevation)

Exclusion Criteria:

   - Prior chemotherapy

   - Prior radiotherapy above the clavicles

   - Prior surgery with curative intent for this disease (complete head and neck exam with
   biopsy allowed)

   - Prior therapy specifically and directly targeting the EGFR pathway

   - Prior severe infusion reaction to a monoclonal antibody

   - Uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled
   hypertension within the past 30 days

   - Concurrent illness likely to interfere with study therapy or to prevent surgical
   resection

   - Pregnant or nursing