Vandetanib to Treat Advanced Kidney Cancer

Exclusion Criteria

• •Prior malignancy of other histology, with the exception of cervical carcinoma in situ or adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient has not required active treatment for more than three years.
• •Patients with VHL disease will be excluded from this study.
• •Patients may not be receiving any other investigational agents or have received treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
• •Patients with known brain metastases (except when adequately treated greater than or equal to 6 months before enrollment with no evidence of recurrence).
• •Use of 5HT-3 antagonists because of the potential effect on corrected Q wave, T wave (QTc) interval.
• •Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes (Appendix C).
• •Drugs listed in Appendix C, Table 2, that in the investigator's opinion cannot be discontinued, are allowed, but must be monitored closely.
• •Clinically significant cardiac event (including symptomatic heart failure, myocardial infarction or angina) within 3 months of entry or presence of any cardiac disease that in the opinion of the Principal Investigator increases the risk of ventricular arrhythmia.
• •Patients with a history a major cardiac event more than 3 months prior to enrolment will be evaluated by a cardiologist to assess cardiac status and potential for increased risk with ZD6474 therapy.
• •History of clinically significant arrhythmia \[including multifocal premature ventricular contraction (PVC), bigeminy, trigeminy, ventricular tachycardia\] that is symptomatic or requires treatment (CTCAE grade 3) or symptomatic/ asymptomatic sustained ventricular tachycardia.
• •Uncontrolled atrial fibrillation. Atrial fibrillation controlled on medication is not excluded.
• •Presence of Left bundle branch block.
• •Previous history of QTc prolongation while taking other medications that required discontinuation of that medication.
• •Congenital long QT syndrome or first degree relative with unexplained sudden death under the age of 40 years.
• •QTc with Bazett's correction that is unmeasurable, or greater than or equal to 480 msec on screening ECG.
• •If a patient has QTc greater than or equal to 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart).
• •The average QTc from the three screening electrocardiograms (ECGs) must be less than 480 msec in order for the patient to be eligible for the study).
• •Patients who are receiving a drug that has a risk of QTc prolongation (see Appendix C, Group/Table 2) are excluded if QTc is greater than or equal to 460 msec.
• •Potassium concentration less than 4.0 mEq/L, calcium (ionized calcium or adjusted for albumin), or magnesium concentrations outside normal limits despite optimal supplementation/correction.
• •Left ventricular ejection fraction less than 45 percent measured by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
• •Hypertension not controlled by medical therapy (systolic blood pressure greater than 150 mmHg or diastolic blood pressure greater than 100 mmHg).
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• •Patient known to be human immunodeficiency virus (HIV)-positive and requiring antiretroviral therapy.
• •Currently active diarrhea that may affect the ability of the patient to absorb ZD6474 or tolerate further diarrhea.
• •Pregnant women are excluded from this study because ZD6474 is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZD6474, breastfeeding should be discontinued if the mother is treated with ZD6474.
• •Any known hypersensitivity to ZD 6474 or other excipients of ZD6474.
• •Concomitant medications that are potent inducers of cytochrome P450 3A4 (CYP3A4) function, such as rifampin, rifabutin, phenytoin, carbamazepine, barbiturates such as phenobarbital, or St. John's Wort.
• •Inclusion of Women and Minorities:
• •Both men and women and members of all races and ethnic groups are eligible for this trial.