Trial of Maintenance SU011248 Versus Placebo Post Chemotherapy Patients With Advanced Urothelial Carcinoma

The primary objective of this study is to compare the progression rate associated with
SU011248 versus Placebo in patients with advanced urothelial carcinoma who have achieved at
least stable disease following combination chemotherapy. Secondary objectives of the trial:
We will explore the safety of SU011248, assess the objective response rate associated with
SU011248 therapy in patients with stable disease after chemotherapy, and assess the median
survival in patients with advanced urothelial carcinoma treated with SU011248 or placebo
following chemotherapy. Correlative objectives of trial: To correlate changes in VEGF and
sVEGFR-2 levels with clinical response in patients with advanced urothelial carcinoma.
Tertiary objective of trial: Determine response and progression rates to SU011248 in patients
crossed over to treatment after placebo.

Inclusion Criteria:

- Histologic/cytologic diagnosis of urothelial carcinoma (tranisitional cell carcinoma
either pure or mixed histology).

- All patients must have received four - six cylces of standard first line chemotherapy
(see appendix A for suggested combinations) for treatment of locally recurrent or
metastatic disease and must have achieved stable disease (SD), partial response (PR),
or complete response (CR) to this chemotherapy.

- Patient must be registered within on month (or the next business day if falls on a
weekend or holiday) of scans demonstrating stable disease or better and no more than
42 days after receiving the last standard chemotherapy dose.

- patients may have received previous adjuvant or neoadjuvant therapy.

- No prior antiangiogenic therapy for this stage of the disease.

- An ECOG performance status of 0-2 and a life expectancy of greater than 6 months.

- If patients received radiation therapy, they must have recovered from side effects
before registration to study.

- No prior malignancy is allowed, except for adequately treated basal cell (or
squamouscell) skin cancer or in situ carcinoma of any site or other adequately treated
malignancy for which the patient is currently disease free for at least one year.
Patients with prostate cancer diagnosed at the time of cystectomy who have an
undetectable PSA without hormonal therapy will be eligible.

- Timing guidelines for pre-study labs and measurements:

- All pre-study labs required for determination of eligibility are to be completed
within 14 days prior to registration.

- X-rays and/or scans used for tumor measurement to determine disease status EKG, and
MUGA are to be completed within one month prior to registration.

- Patients must have adequate organ and marrow function as defined below obtained within
14 days from registration.

- All patients must be informed of the investigational nature of this study and must
sign an informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria

- Major surgery within 4 weeks of starting the study treatment.

- NCI CTCAE grade 3 hemorrhage or higher within 4 weeks of starting the study treatment.

- History of or known spinal cord compression, or carcinomatous meningitis, or evidence
of symptomatic brain or leptomeningeal disease on screening CT or MRI scan. However
treated, stable and asymptomatic brain metastases are allowed.

- Known HIV - positive patients may not participate. This is to avoid additional
complications that immune supression and HIV infection may cause due tothe intense
nature of the chemotherapy in this trial.

- Any of the following within the 6 months prior to the study drug
administration:myocardial infraction, severe/unstable angina, coronary/peripheral
artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular
accident or transient ischemic attack, pulmonary embolism.

- Ongoing cardiac dysrhythmias of NCI CTCAE grade >2.

- Patients with history of who are suspected to have CHF can be included as long as they
are asymptomatic and have an ejection fraction that is equal to or above the
institutional lower limit of normal by baseline MUGA.

- QTc interval> 500 msec on baseline EKG.

- Hypertension that cannot be controlled by medications (>150/11 mm Hg despite optimal
medical therapy).

- Patients with pre-existing thyroid function abnormalities that can not be controlled
medically.

- Patients may not have unresolved bacterial infection.

- Concurrent treatment on another clinical trial. Supportive care trials or
non-treatment trials, e.g. QOL, are allowed.

- Pregnancy or brestfeeding. Female subjects must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of
therapy. All female subjects with reproductive potential must have a negative
pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically
sterile or must agree to use effective contraception during the period of therapy. The
definition of effective contraception will be based on the judgement of the principal
investigator or a designated associate.

- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormally that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgement of the investigator would make the subject inappropriate for entry into
thid study.