Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC

OUTLINE: This is a multi-center study.

- Gemcitabine ( 1000 mg/m2) IV days 1 and 8

- Cisplatin (70 mg/m2) IV day 1 and

- Sunitinib malate (37.5 mg) oral daily for days 1-14

The treatment regimen will be administered in four, 21-day, cycles followed by radical
cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib
malate.

ECOG performance status 0 or 1

Hematopoietic:

- Absolute Neutrophil Count (ANC) > 1.5 K/mm3 [(IS): 1.5 x 109/L]

- Platelets > 100 K/mm3 [(IS): 100 x 109/L]

- Hemoglobin (Hgb) > 9.0 g/dL [(IS): 90 g/L]

Hepatic:

- Total bilirubin < 1.5 x Upper Limit of Normal (ULN)

- Aspartate aminotransferase (AST) ≤ 2.5 x ULN

- Alanine aminotransferase (ALT) ≤ 2.5 x ULN

Renal:

- Calculated creatinine clearance of > 60 cc/min

Cardiovascular:

- No uncontrolled angina, congestive heart failure or myocardial infarction or
coronary/peripheral artery bypass graft within 6 months prior to registration for
protocol therapy.

Inclusion Criteria:

- Histological proof of muscle-invasive transitional cell carcinoma of the bladder
(stage II-III) with no evidence of metastatic disease (focal squamous and/or
adenocarcinoma differentiation allowed, sarcomatoid and small-cell components not
allowed). Patient with any degree of fixation of the pelvic sidewall are not
eligible.

- Must be willing to undergo a cystoscopy if tumor block is not available prior to
registration for protocol therapy.

- Eligible for radical cystectomy as per the attending urologist.

- Prior radiation therapy to bone marrow is allowed to < 25% of the marrow, and must be
completed at least 6 months prior to registration for protocol therapy

- Written informed consent and HIPAA authorization for release of personal health
information.

- Age > 18 years at the time of consent.

- Females of childbearing potential and males must be willing to use an effective
method of contraception (hormonal or barrier method of birth control; abstinence)
from the time consent is signed until 6 weeks after treatment discontinuation.

- Females of childbearing potential must have a negative pregnancy test within 7 days
prior to being registered for protocol therapy.

Exclusion Criteria:

- No prior radiotherapy to the pelvis.

- No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, Gleason< grade 7 prostate cancers, or
other cancer for which the patient has been disease-free for at least 5 years.

- No treatment with any investigational agent within 30 days prior to registration for
protocol therapy.

- No cerebrovascular accident or transient ischemic attack within 6 months prior to
registration for protocol therapy.

- No evidence of pulmonary embolism within 6 months prior to registration for protocol
therapy.

- No uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy).

- No evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2.

- No history of uncontrolled/untreated thyroid dysfunction.

- No prolonged QTc interval (> 450 msec) on pre-entry electrocardiogram obtained within
28 days prior to being registered on study.

- Patients on warfarin (>2mg) for thrombosis must be able and willing to switch to low
molecular weight heparin prior to registration for protocol therapy.

- No use of drugs having proarrhythmic potential (terfenadine, quinidine, procainamide,
disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and
flecainide) within 7 days prior to registration for protocol therapy.

- No use of CYP3A4 inhibitors (see section 5.3 for a list) within 7 days of
registration for protocol therapy.

- No use of CYP3A4 inducers (see section 5.3 for a list) within 14 days of registration
for protocol therapy.

- No use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol
therapy.

- Females must not be breastfeeding.