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

A Phase II Trial of Neoadjuvant Cisplatin, Gemcitabine and Sunitinib Malate Followed by Radical Cystectomy for Transitional Cell Carcinoma (TCC) of the Bladder: Hoosier Oncology Group GU07-123

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.