Docetaxel in Combination With Zactima (ZD6474) in Patients With Locally Advanced Squamous Cell Carcinoma of the the Head and Neck

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.