Cetuximab, Carboplatin, and Paclitaxel Followed by Radiation Therapy, With or Without Cisplatin, in Treating Patients With Metastatic Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: Cetuximab; Carboplatin; Paclitaxel; Conventional Surgery; Radiation Therapy
Intervention description: Beginning weekly dose 400 mg/m^2 IV over 1-2 hours, and 250 mg/m^2 weeks 2-6.; AUC 2 weekly for 6 courses.; 135 mg/m^2 weekly for 6 courses.; Following induction in second part of study.; Following induction in second part of study.
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: 48.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: stage IV squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the lip and oral cavity

Summary:

      RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different
      ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others
      interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy,
      such as carboplatin, 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. Giving more than
      one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses
      high-energy x-rays and other types of radiation to kill tumor cells. Giving cetuximab
      together with combination chemotherapy and radiation therapy, with or without cisplatin, may
      kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cetuximab together with carboplatin
      and paclitaxel followed by radiation therapy, with or without cisplatin, works in treating
      patients with metastatic head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histological proof (from the primary lesion and/or lymph nodes) of
             squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or
             larynx.

          2. Patients should have stage IV disease, stage T0-4 N2b/2c/3 M0 (for nasopharynx
             patients, stage N1 disease is eligible). Measurable disease by Response Evaluation
             Criteria in Solid Tumors (RECIST) is required.

          3. Patients with stage Tx primary disease are eligible if there is N2b/3 adenopathy.

          4. Karnofsky performance status of >/= 80 or Eastern Cooperative Oncology Group (ECOG)
             point scale 0-1

          5. Age > 16 years

          6. Patients should have adequate bone marrow function defined as an absolute peripheral
             granulocyte count (AGC) of > 1500 cells/mm3 and platelet count of > 100,000 cells/mm3;
             adequate hepatic function with bilirubin </= Upper Limit of Normal (ULN), aspartate
             aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) may be up to
             2.5 times the upper limit of normal if alkaline phosphatase is normal. Alkaline
             phosphatase may be up to 4* ULN if SGPT and SGOT are normal. Patients who have both
             SGPT and SGOT > 1.5 ULN and alkaline phosphatase > 2.5 * ULN are not eligible. Normal
             PT/PTT and normal serum calcium (without intervention) are required.

          7. Creatinine clearance > 40 ml/min determined by 24 hour collection or nomogram: CrCl
             male = (140 - age) times (weight in kg)/serum Cr times 72 CrCl female = 0.85 times
             (CrCl male)

          8. Patients should have no serious acute or chronic co-morbid condition, or acute
             infection.

          9. Patients must sign a study-specific informed consent form.

        Exclusion Criteria:

          1. Histology other than squamous cell carcinoma.

          2. Evidence of distant metastases (below the clavicle) by clinical or radiographic means.

          3. Karnofsky performance status < 80 or ECOG>1

          4. Prior chemotherapy, within the previous 3 years.

          5. Prior radiotherapy to the head and neck.

          6. Prior cetuximab therapy, prior therapy with any other drug that targets the EGFR
             pathway, or prior therapy with a murine or chimeric monoclonal antibody.

          7. Initial surgical resection rendering the patient clinically and radiologically disease
             free.

          8. Simultaneous primary invasive cancers.

          9. Patients with another malignancy (excluding non melanoma skin cancers, and cancers
             treated > 3 years prior for which patient remains continuously disease free).

         10. Women of childbearing potential (WOCBP) who are unwilling or unable to use an
             acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks
             after the study. Subjects who are men must also agree to use effective contraception.
             WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to
             the start of study medication.

         11. WOCBP using a prohibited contraceptive method.

         12. Women who are pregnant or breastfeeding.

         13. Women with a positive pregnancy test on enrollment or prior to study drug
             administration.

         14. Refusal to sign the informed consent.

         15. Pre-existing peripheral neuropathy Common Terminology Criteria for Adverse Events
             (CTCAE) grade 2 or worse.