Phase II Study of Concurrent C225, Cisplatin and Radiation in Stage IV Squamous Cell Carcinoma of the Head and Neck
Condition: Head and Neck Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: cetuximab C225; cisplatin; radiation therapy
Intervention description: 400 mg/m^2 IV over 120 minutes on Day 1, 250 mg/m^2 IV over 60 minutes on Day 8, then weekly; 75 mg/m^2 IV over 30-60 minutes starting day 15 every 3 weeks * 3 (Days 1, 22, and 43 of radiation therapy (RT)); RT 70 Gy / 35 starting Day 15, 200cGy / d * 7 weeks (35 fractions)
Intervention MeSH terms: Cisplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the oropharynx

Summary:

      RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill
      them or deliver tumor-killing substances to them without harming normal cells. Drugs used in
      chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so
      they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.
      Cetuximab may make the tumor cells more sensitive to radiation therapy and chemotherapy.
      Giving monoclonal antibody therapy together with chemoradiotherapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together
      with radiation therapy works in treating patients with locally advanced or regional stage IV
      head and neck cancer that cannot be removed by surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed squamous cell or undifferentiated carcinoma of the head and
             neck (excluding nasopharynx, paranasal sinus, and parotid gland)

               -  Unresectable locally advanced or regional stage IV disease

               -  No evidence of distant metastases

          -  Must have demonstrable primary tumor site

          -  Measurable disease

          -  Unresectable disease

               -  Meets the following criteria for unresectable disease by tumor site:

                    -  Hypopharynx, meeting 1 of the following criteria:

                         -  Extension across the midline of the posterior pharyngeal wall

                         -  Any evidence of fixation to the cervical spine

                    -  Larynx

                         -  Direct subglottic extension (>3cm) into surrounding muscle or skin

                    -  Oral cavity

                         -  Lesion precluding functional reconstruction

                    -  Base of tongue, meeting 1 of the following criteria:

                         -  Extension into the root of the tongue

                         -  Patient refuses total glossectomy

                    -  Tonsillar area, meeting 1 of the following criteria:

                         -  Extension into pterygoid area as manifested by x-ray or trismus

                         -  Extension across midline of pharyngeal wall

                         -  Direct extension into soft tissue of the neck

                    -  Unilateral neck node metastases fixed to carotid artery, mastoid, base of
                       skull, or cervical spine with any of the above tumors

          -  Patients requiring total glossectomy are eligible

          -  Age>=18 years

          -  ECOG Performance status of 0-1

          -  Adequate hematologic, renal, and hepatic function obtained <=4 weeks prior to
             registration

               -  Absolute neutrophil count ≥ 2,000/mm^3

               -  Platelet count ≥ 100,000/mm^3

               -  Hemoglobin ≥ 9.0 g/dL

               -  Alkaline phosphatase ≤ 3 times normal

               -  Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤ 3 times
                  normal

               -  Bilirubin ≤ 1.5 mg/dL

               -  Creatinine ≤ 1.2 mg/dL OR creatinine clearance ≥ 50 mL/min

          -  Able to tolerate fluid load

          -  At least 14 days since major surgery (including dental extraction) except percutaneous
             endoscopic gastrostomy (PEG) placement or mediport placement

        Exclusion Criteria:

          -  Pregnant or nursing

          -  Fertile patients do not use effective contraception

          -  Patients who refuse surgery but whose tumors are technically resectable OR whose
             tumors are unresectable for medical reasons are not eligible

          -  Disease metastases below the clavicles or elsewhere (M1) or with a postoperative
             recurrence

          -  Prior excisional surgery of head and neck tumor

          -  Prior radiotherapy to the head and neck region

          -  Prior chemotherapy

          -  Prior drugs that target the epidermal growth factor receptor pathway

          -  Prior chimerized or murine monoclonal antibody

          -  Active systemic infection

          -  Known allergy to murine proteins

          -  Severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the
             past year

          -  Myocardial infarction within the past 3 months

          -  Uncontrolled congestive heart failure

          -  Unstable or uncontrolled angina

          -  Clinically apparent jaundice

          -  Postoperative recurrence

          -  Other malignancy within the past 3 years except resected basal cell or squamous cell
             skin cancer, carcinoma in situ of the cervix, or other in situ tumors