Docetaxel in Combination With Zactima (ZD6474) in Patients With Locally Advanced Squamous Cell Carcinoma of the the Head and Neck
Condition: Squamous Cell Carcinoma of Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: ZD6474; Docetaxel
Intervention description: Taken orally once every morning; Given on the first day of every treatment cycle (every 3 weeks)
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCCHN

Summary:

      In this research study, the researchers are comparing the combination of docetaxel and
      Zactima with docetaxel alone to see if the combination of the two drugs will be more
      effective than docetaxel alone. Zactima blocks the actions of three substances in the body:
      1)vascular endothelial growth factor reception (VEGFR); 2)epidermal growth factor receptor
      (EGFR); and 3) rearranged during transfection (RET). VEGFR stimulates the growth of new blood
      vessels. When certain proteins bind to the VEGF receptor, a process begins to occur which
      allows new blood vessels to be made that provide blood to the cancer cells. Zactima is
      thought to block these proteins from binding to the VEGF receptor, which would then block the
      process that creates new blood vessels. EGFR controls how quickly cells grow and multiply.
      RET is thought to have a particularly significant role in the development and growth of
      squamous cell tumors. The actions of Zactima are very different from the way standard
      chemotherapy drugs work. Researchers believe that Zactima might have different side effects
      from other cancer treatments so another one of the purposes of this study is to assess the
      side effects caused by the drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically documented SCCHN, excluding nasopharyngeal carcinoma.
             Squamous cell carcinomas of unknown primary are allowed. Primary salivary gland tumors
             and tumor of the nasal cavity and paranasal sinuses are not included.

          -  18 years of age or older.

          -  Evaluable or uni-dimensionally measurable local-regional and/or metastatic disease
             that is not amendable to primary surgical resection or radiotherapy.

          -  Life expectancy of at least 3 months.

          -  ECOG performance status of 0-2.

          -  Negative pregnancy test for women of childbearing potential.

          -  Adequate bone marrow function.

        Exclusion Criteria:

          -  Evidence of sever or uncontrolled systemic disease or any concurrent condition which
             in the investigator's opinion makes it undesirable for the patient to participate in
             the trial.

          -  Clinically significant cardiac event such as myocardial infarction, NYHA
             classification of heart disease grade II or higher within 3 months of study entry, or
             presence of cardiac disease that, in the opinion of the investigator, increases the
             risk of ventricular arrhythmia.

          -  History of arrhythmia which is symptomatic or requires treatment or asymptomatic
             sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is
             not excluded.

          -  Previous history of QTc prolongation as a result from other medication that required
             discontinuation of that medication.

          -  Congenital long QT syndrome, or 1st degree relative with unexplained sudden death
             under 40 years of age.

          -  Presence of left bundle branch block.

          -  QTc with Bazett's correction that is unmeasurable or > 480 msec on screening ECG.

          -  Any concomitant medication that may cause QTC prolongation, induce Torsades de Pointes
             or induce CYP3A4 function.

          -  Hypertension not controlled by medical therapy.

          -  Currently active diarrhea that may affect the ability of the patient to absorb
             Zactima.

          -  Pregnant or breast-feeding women.

          -  Previous or concurrent malignancies of other histologies within the last 5 years, with
             the exception of cervical carcinoma in-situ and adequately treated basal cell or
             squamous cell carcinoma of the skin.

          -  Receipt of any investigational agents within 30 days prior to commencing study
             treatment.

          -  Prior treatment with docetaxel.

          -  Last dose of prior chemotherapy discontinued less than 3 weeks before start of study
             therapy.

          -  Last dose of radiation therapy within the last 4 weeks before the start of study
             therapy, except palliative radiotherapy.

          -  Major surgery within 4 weeks, or incompletely healed surgical incision.