Inclusion Criteria

- INCLUSION CRITERIA:

Patients must meet all the following criteria to be eligible for study enrolment:

Histologically confirmed clear cell renal cell carcinoma (to be confirmed at the Dept. of
Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI)).

Patients must have advanced disease (metastatic or unresectable) disease.

Measurable disease, defined as at least one lesion that can be accurately measured in at
least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm
with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.

See section 6.2 for the evaluation of measurable disease.

Prior therapy:

1. All patients must have either received prior sunitinib or sorafenib (discontinued for
disease progression or unacceptable toxicity) or be unable to receive these agents.
Patients who have discontinued sunitinib or sorafenib for life threatening toxicities
that are also known to occur with vandetanib (such as skin, GI toxicities, bowel
perforation etc.) will not be eligible.

2. All patients must have failed high dose IL-2, be ineligible to receive this agent or
decline this therapy.

Age greater than or equal to 18 years.

Life expectancy greater than 3 months.

Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.

Patients must have normal organ and marrow function as defined below: white blood
cell (WBC) count greater than or equal to 3,000/microL, absolute neutrophil count
greater than or equal to 1,500/microL, platelet count greater than or equal to
100,000/microL, 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, aspartate aminotransferase (AST) and alanine aminotransferase (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 principal
investigator (PI))

Recovery from acute toxicity of prior treatment for RCC (to less than or equal to
grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v3.0).

At least 4 weeks from completion of major surgery and a healed surgical incision.

Negative pregnancy test in female patients of childbearing potential within 7 days of
enrollment.

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

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.