neoadjuvant cisplatin, gemcitabine, sunitinib malate + radical cystectomy for tcc

Conditions: Transitional Cell Carcinoma of the Bladder

Summary: 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.

Eligibility criteria:
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.

Keywords: tcc