Induction Chemo Then Concurrent Chemoradiotherapy With Cetuximab in Locally Advanced Head and Neck Squamous Cell Cancer
Condition: Head and Neck Squamous Cell Cancer
MeSH terms: Neoplasms, Squamous Cell; Carcinoma, Squamous Cell
Intervention: Cetuximab
Intervention description: Single arm phase II study of chemotherapy
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head; Neck; Locally advanced; Squamous Cell; Hypopharynx; Larynx; Oral Cavity; Base of Tongue; Tonsil; Neck lymph node; Resection

Summary:

      This is an open label, single arm Phase II study of induction chemotherapy followed by
      concurrent chemo-radiotherapy in patients with locally advanced head and neck squamous cell
      cancer (HNSCC) using monoclonal antibody cetuximab. Those patients with locally advanced
      HNSCC deemed to be candidates for definitive concurrent chemo-radiotherapy will be treated
      initially with 6 weeks of PCC (Paclitaxel, cetuximab and Carboplatin). This will be followed
      by a week of no treatment for interim evaluation, followed by definitive concurrent
      chemo-radiotherapy using 70Gy radiation with weekly cetuximab and cisplatin for 7 weeks. The
      hypothesis of the study is that the use of cetuximab during induction chemotherapy followed
      by cetuximab concurrent with chemoradiotherapy using low dose weekly cisplatin will improve
      local control as well as distant spread.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult patients 18 years and older with histologically proven locally advanced stage
             III or IV unresectable Squamous cell head and neck cancer SCCHN (including cancers of
             oral cavity, oropharynx, larynx and hypopharynx) with no evidence of distant
             metastasis

          2. A careful evaluation for resection is required from the surgeon and criteria for
             unresectability carefully defined for individual primary sites as follows:

               -  Hypopharynx: The tumor must extend across the midline of the posterior pharyngeal
                  wall or be fixed to the cervical spine

               -  Larynx: There must by either direct extension into surrounding muscle or skin or
                  greater than 3 cm of sub-glottic extension

               -  Oral cavity: The lesion must be so extensive that a functional reconstruction is
                  not possible.

               -  Base of Tongue: The tumor must extend into the roof of tongue, or the patient
                  must refuse a recommended total glossectomy

               -  Tonsil: The tumor must extend into the pterygoid region as manifested by clinical
                  trismus or demonstrated across the midline of the pharyngeal wall or directly
                  into soft tissue of the neck

               -  Patients with neck lymph node metastases fixed to the carotid artery, the
                  mastoid, the base of the skull, or the cervical spine are considered
                  un-resectable

               -  Medical unsuitability for resection is not sufficient for patient eligibility

               -  Patient's refusal for surgery except in case of total glossectomy is not
                  considered a reason for unresectibility

          3. Patients must have received no prior treatment for head and neck cancer

          4. ECOG Performance status 0-1

          5. Adequate organ function (All labs should be obtained within 14 days prior to start of
             study drug treatment)

               -  leukocytes > 3,000/mcL

               -  absolute neutrophil count > 1,500/mcL

               -  platelets > 100,000/mcL

               -  total Bilirubin within normal institutional limits

               -  AST (SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

               -  creatinine within normal institutional limits or creatinine clearance > 60
                  mL/min/1.73 m2 for patients with creatinine levels above institutional normal

          6. Ability to give informed consent and willingness to adhere to study protocol

          7. Subjects of reproductive potential must agree to follow accepted birth control methods
             during treatment and for 12 months after completion of treatment. Female subject is
             either post-menopausal or surgically sterilized or willing to use an acceptable method
             of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
             birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
             spermicide, condom with spermicide, or abstinence) for the duration of the study

        Exclusion Criteria:

          1. Patient who have had prior treatment for head and neck cancer

          2. Prior history of radiation to head and neck area

          3. Known malignancy other than the current cancer

          4. Uncontrolled intercurrent illness including but not limited to ongoing active
             infection, history of cardiac disease, e.g. uncontrolled hypertension, unstable
             angina, congestive heart failure, myocardial infarction within last six months or
             ventricular arrhythmias requiring medication, psychiatric illness that would impair
             patients ability to comply with study requirements

          5. Pregnant or lactating women (any women becoming pregnant during the study will be
             withdrawn from the study)

          6. Patient with documented or symptoms of peripheral neuropathy

          7. History of allergic reaction to compounds similar to the ones used in this study

          8. Any condition that would hamper ability to give informed consent or ability to comply
             with study protocol

          9. HIV patients on anti-retroviral therapy are in-eligible to participate in this study
             because of potential interaction with the study drugs and increase susceptibility for
             infections during course of marrow suppressive chemotherapy and radiotherapy