Induction Chemotherapy Followed By Cetuximab and Radiation in HPV-Associated Resectable Stage III/IV Oropharynx Cancer
Condition: Head and Neck Cancer; Precancerous Condition
MeSH terms: Precancerous Conditions
Intervention: cetuximab; intensity-modulated radiation therapy (IMRT); Paclitaxel; Cisplatin
Intervention description: Given IV; Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy; Given IV, 90 mg/m^2 on days 1, 8 and 15; Given IV, 75 mg/m^2 on day 1
Intervention MeSH terms: Paclitaxel; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: human papilloma virus infection; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; tongue cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways.
      Some block the ability of tumor cells to grow and spread. Others find tumor cells and help
      kill them or carry tumor-killing substances to them. Radiation therapy uses high energy
      x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with
      radiation therapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well
      they work when followed by cetuximab and two different doses of intensity-modulated radiation
      therapy in treating patients with HPV-associated stage III or stage IV cancer of the
      oropharynx that can be removed by surgery.
    

Eligibility criteria:

        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