Radiation Therapy (XRT) and ZD6474 in Non-Small Cell Lung Cancer (NSCLC)

Exclusion Criteria

• •1. Pregnancy or breast feeding
• •2. Bronchoalveolar carcinoma
• •3. Oxygen saturation less than 90% on room air or requirement for oxygen supplementation
• •4. Any condition that is likely to interfere with regular follow-up
• •5. Patient cannot have participated in any clinical trial involving conventional or investigational drugs within 4 weeks prior to administration of ZD6474
• •6. Patient cannot have received radiation therapy or chemotherapy within 4 weeks prior to administration of ZD6474 (6 weeks for nitrosoureas and mitomycin)
• •7. Patient cannot be receiving herbal remedies or other over-the-counter biologics (e.g., shark cartilage)
• •8. Patient cannot be receiving drugs with known significant 3A4 inhibitory effects (e.g., ketoconazole, erythromycin, and verapamil)
• •9. Patient cannot be receiving drugs with known corneal toxicology (e.g., tamoxifen, chlorpromazine, amiodarone, and chloroquine)
• •10. Patients cannot have received previous treatment with agents that block the EGF or VEGF pathways
• •11. Patient cannot have serum calcium levels below the lower limits of normal.
• •12. Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease \>/=2 (see Appendix J) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• •13. History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events (CTCAE) grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• •14. QTc with Bazett's correction that is unmeasurable, or \>/= 480 msec on screening Electrocardiograph (ECG/EKG). If a patient has QTc \>/= 480 msec on screening EKG, the screening EKG may be repeated twice (at least 24 hours apart). The average QTc from the three screening EKGs must be \<480 msec in order for the patient to be eligible for the study.
• •15. Patients cannot have a history of QT prolongation with other medication
• •16. Patients cannot have a congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
• •17. Any concomitant medications that affect QTc or induce Torsades de Pointes and cannot be discontinued
• •18. Left ventricular ejection fraction less than 45% measured by multigated blood-pool imaging (MUGA) or Echocardiogram for subjects with previous anthracycline therapy (total dose greater than 450 mg/m2) or significant cardiovascular disease
• •19. Patients cannot have a severe hypersensitivity reaction to drugs formulated with polysorbate 80
• •20. Patients cannot have any evidence of severe or uncontrolled systemic disease, including known Hepatitis B or HIV infection. Screening for chronic conditions is not required, although subjects known to have such conditions should not be enrolled.
• •21. Patient cannot have had any active cancer in addition to their current lung cancer within the last 3 years with the exception of superficial skin cancer (e.g., basal cell or squamous cell carcinoma)
• •22. Patient cannot have any central nervous system (CNS) metastases, unless treated at least 4 weeks before entry, and stable without steroid treatment for 1 week
• •23. Patient cannot have any additional uncontrolled serious medical or psychiatric illness
• •24. Patients with other contraindication for radiation therapy as decided by the physician
• •25. Patients cannot have presence of a left bundle branch block (LBBB).
• •26. Hypertension not controlled by medical therapy (systolic blood pressure \> 140 mm Hg or diastolic blood pressure \> 90 mm Hg)
• •27. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy