Evaluation of Cetuximab (ERBITUX) and Concurrent Carboplatin, Paclitaxel & Radiotherapy in the Management of Patients With Advanced Locoregional Squamous Cell Carcinomas of the Head and Neck (GCC 0442)
Condition: Cancer of Head and Neck
MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
Intervention: Erbitux, Paclitaxel & Carboplatin; Radiation
Intervention description: Paclitaxel, 40 mg/m2/week,
1-hour infusion (weeks 2-9.Paclitaxel will be administered on a weekly schedule at a dose of 40mg/m2 IV by 1-hour infusion prior to cetuximab dose.
Cetuximab: 400 mg/m2 IV (initial dose) week 1 then 250 mg/m2 IV weekly for 8 weeks weeks 2-9). Cetuximab will be administered 400mg/m2 IV on Day 1, then the first 250 mg/m2 IV dose will be given on day 8 (week 2) prior to carboplatin dose.
Carboplatin, AUC=2/week as a 30 minute infusion after cetuximab infusion (weeks 2-9)Carboplatin will be administered at a dose of AUC = 2/week IV bolus each week and will be administered prior to head and neck irradiation dose. (Carboplatin: AUC=2/week x 8 weeks (weeks 2-9); XRT=Radiotherapy 1.8 Gy radiation/day, 5 days a week for a total of 70.2 Gy.(weeks 2-9) - IMRT is allowed
Intervention MeSH terms: Paclitaxel; Carboplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Neoplasms

Summary:

      The purpose of this study is to evaluate the response of the tumor to the treatment regimen
      that will be used in this study. This study will also test the safety of cetuximab (C225),
      given with chemotherapy and radiation therapy. We also want to see what effects (good and
      bad) cetuximab, chemotherapy, and radiation therapy have head & neck cancer.

      C225 has been designed to stop the growth of the tumor by blocking certain chemical pathways
      that lead to tumor cell growth. In prior studies with head & neck cancer patients, C225 has
      delayed tumor growth and provided relief of symptoms in some patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically proved locally advanced squamous cell carcinoma of the head and neck of
             all primary sites. The following TNM stages by sites will be eligible.Oral cavity,
             Pharynx, Larynx, Nasopharynx, paranasal sinuses, Oral cavity, Pharynx, Larynx,
             Nasopharynx, paranasal sinuses- T4 N0 N1 N2-A,B,C N3, T3 N0 N1 N2-A,B,C N3 Any T
             N2-A,B,C N3 Unknown primary Tx N2-A,B,C N3 Note: Only clearly unresectable T4 N0
             lesions are eligible for study provided the reasons for unresectability are due to
             extensive anatomic involvement and are outlined by the surgeon

          2. Patients must have signed an approved informed consent.

          3. Patients with Performance Status 0-2.

          4. No evidence of distant metastatic disease.

          5. No previous radiation therapy.

          6. No previous chemotherapy.

          7. Patients must be greater than 18 years of age.

          8. Women of child bearing potential (WOCBP) must have a negative pregnancy test within 7
             days of treatment. Patients are considered not of child bearing potential if they are
             surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or they are postmenopausal.

          9. Pretreatment evaluations include:

             History and physical examination within four weeks prior to study entry Dental
             evaluation Medical oncology examination to evaluate medical contraindications prior to
             start of chemotherapy

         10. Adequate renal & bone marrow function determined by the following laboratory
             parameters:

             ANC greater than or equal to 1500/mm3; platelets greater than or equal to 100,000/mm3;
             hemoglobin greater than or equal to 8.0 g/dl; Serum Creatinine less than or equal to
             2.0 mg/dl, Total bilirubin less than 1.5 X the ULIN; AST/ALT less than 3 times the
             ULN, Creatinine Clearance greater than or equal to 50 cc/min

         11. Evidence of measurable disease.

         12. No evidence of concomitant malignancy except for non-melanomatous skin cancer
             (controlled or controllable) or carcinoma in situ of the cervix.

        Exclusion Criteria:

        Any of the following criteria will make the patient ineligible to participate in this
        study:

          1. Acute hepatitis or known HIV.

          2. Active or uncontrolled infection.

          3. Significant history of concomitant life threatening / uncontrolled cardiac disease;
             i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within
             prior 6 months), uncontrolled congestive heart failure, and known cardiomyopathy with
             decreased ejection fraction, cardiac arrhythmia

          4. Prior therapy which specifically and directly targets the EGFR pathway.

          5. Prior severe infusion reaction to a monoclonal antibody.

          6. Any concurrent chemotherapy not indicated in the study protocol or any other
             investigational agent(s).

          7. Women of childbearing potential (WOCBP) and male participants who are unwilling or
             unable to use an effective method to avoid pregnancy for the entire study period

          8. Preexisting clinically significant neuropathy.

          9. Patients with loco-regional recurrences from any site with no prior radiation therapy
             and not amenable for salvage surgery are not eligible for study.