Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC
Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC
This trial will investigate the activity of sunitinib combined with cisplatin and gemcitabine
 followed by radical cystectomy in patients with Transitional Cell Carcinoma (TCC) of the
 Bladder.
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.