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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Transitional Cell Carcinoma of the Bladder

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Cisplatin
* Drug: Sunitinib Malate
* Procedure: Radical Cystectomy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Treatment<br>Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy | Drug: Gemcitabine<br>* Gemcitabine ( 1000 mg/m2) IV days 1 and 8<br>Drug: Cisplatin<br>* Cisplatin (70 mg/m2) IV day 1<br>Drug: Sunitinib Malate<br>* Sunitinib malate (37.5 mg) oral daily for days 1-14<br>Procedure: Radical Cystectomy<br>* Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) Rate. | number of participants with a pCR | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile | Evaluate the safety profile of Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy in participants with TCC | 18 months | 
| Objective Response Rate | To determine the objective response rate for patients with measurable disease according to RECIST. | 18 months | 
| Progression Free Survival |  | 18 months | 
| Correlate Biomarker Expression | To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TCC