Inclusion Criteria

- INCLUSION CRITERIA:

Patients must satisfy all the following criteria to be eligible for study enrolment.

Clinical diagnosis of von Hippel Lindau disease.

The presence of at least one measurable (as defined by RECIST) renal tumor (RCC). Patients
with tumors localized to the kidney as well as those with metastatic RCC are eligible.

Age greater than or equal to 18 years.

Life expectancy greater than 3 months

Performance status ECOG 0-2.

Patients must have normal organ and marrow function as defined below: WBC count greater
than or equal to 3,000micro/L, absolute neutrophil count greater than or equal to 1,500
micro/L platelet count greater than or equal to 100,000 micro/L, serum creatinine less
than or equal to 1.5 times upper limit of reference range or measured 24 hr. creatinine
clearance greater than or equal to 50 ml/min, AST and ALT less than 2.5 times upper limit
of reference range, total bilirubin less than 1.5 times upper limit of reference range (
less than 3 times upper limit of reference range in patients with Gilbert's disease),
alkaline phosphatase less than or equal to 2.5 times upper limit of reference range (or
less than or equal to 5 times upper limit of reference range if considered to be related
to liver metastases by the PI).

No history of serious intercurrent medical illness.

At least four weeks from completion of any other surgical or investigational therapy for
von Hippel Lindau and at least 4 weeks from any major surgical procedure. In addition,
patients who have undergone recent major surgery should have well healed surgical
incisions.

All men and women of childbearing potential must use effective contraception.

Negative pregnancy test in female patients of childbearing potential within 7 days prior
to enrolment on study

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Prior or concomitant non-von Hippel Lindau associated malignancy with the exception of
adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in
situ or any other malignancy from which the patient has remained disease free for more
than five years.

Known brain metastases (unless adequately resected or irradiated with no evidence of
recurrence for at least 6 months).

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the
study or those who have not recovered from adverse events (to less than or equal to grade
1 CTCAE v3.0) due to agents administered more than 4 weeks earlier.

Patients may not be receiving any other investigational agents or have received treatment
with a non-approved or investigational drug within 4 weeks prior to Day 1 of study
treatment except those used for imaging studies.

Use of 5HT-3 antagonists because of the potential effect on QTc interval.

Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes.

Concomitant medications that are potent inducers of CYP3A4 function, such as rifampin,
rifabutin, phenytoin, carbamazapine, barbiturates such as phenobarbital, or St. John's
Wort.

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.

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 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 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 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 HIV positive and requiring antiretroviral therapy.

Currently active diarrhea that may affect the ability of the patient to absorb ZD6474 or
tolerate further diarrhea.

Patients on therapeutic anticoagulation

Patients with known bleeding disorders

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 ZD6474 or other excipients of ZD6474.