Cisplatin, Bevacizumab, and Gemcitabine Followed by Surgery, Bevacizumab, and Paclitaxel in Treating Patients With Locally Advanced Nonmetastatic Bladder Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin, gemcitabine, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving cisplatin, bevacizumab, and gemcitabine followed by surgery, bevacizumab, and paclitaxel works in treating patients with locally advanced nonmetastatic bladder cancer that can be removed by surgery.

Official Title
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A Phase II Study of Neo-Adjuvant Cisplatin, Gemcitabine & Bevacizumab, Followed by Radical Cystectomy for Patients With Muscle Invasive, Resectable, Non-Metastatic Transitional Cell Carcinoma (TCC) of the Bladder

Conditions
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Bladder Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Procedure: cysectomy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell cancer (TCC) of the bladder Staged as follows: Muscle invasive (T2-T4a) Node negative (N0) No histologically or cytologically proven lymph node metastases Nonmetastatic (M0) No evidence of distant metastases Resectable disease Able to begin protocol treatment within 6 weeks after transurethral resection and cystoscopic evaluation No central nervous system or brain metastases PATIENT CHARACTERISTICS: ECOG performance status of 0-2 Karnofsky 60-100% White blood cell count ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 AST(SGOT) and ALT(SGPT) ≤ 2 times upper limit of normal Bilirubin ≤1.5 mg/dL Creatinine clearance ≥ 60 mL/min Urine protein/creatinine ratio < 1.0 Blood pressure ≤150/100 mm Hg No prohibitive medical risks for chemotherapy No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine hydrochloride, or paclitaxel No unstable angina No history of myocardial infarction within the past 6 months No cardiac arrhythmias No New York Heart Association (NYHA) congestive heart failure ≥ grade 2 No history of stroke within the past 6 months No clinically significant peripheral vascular disease No evidence of bleeding diathesis or coagulopathy No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious nonhealing wound, ulcer, or bone fracture No psychiatric illness or other psychosocial situation that would limit ability to comply with study and/or follow-up procedures Not pregnant or nursing Negative pregnancy test Fertile patients must agree to use adequate contraception prior to study entry and for the duration of study participation No significant traumatic injury with in the past 28 days PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy No prior pelvic radiation therapy More than 4 weeks since prior participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study No concurrent participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study No major surgical procedure or open biopsy within the past 28 days No anticipation of need for major surgical procedure during the course of the study No minor surgical procedures, fine-needle aspirations, or core biopsies within the past 7 days No concurrent treatment with hormones or other chemotherapeutic agents except the following: Steroids given for adrenal failure Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) Intermittent use of dexamethasone as an antiemetic in solid tumor protocols No other concurrent investigational or commercial agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: study intervention<br>Neo-adjuvant cisplatin, gemcitabine and bevacizumab followed by radical cystectomy. Patients without residual disease will enter follow up after surgery. Patients with residual disease will receive adjuvant therapy with bevacizumab and ciaplatin. | Biological: bevacizumab<br>* Before surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 4 cycles After surgery: given as a 15mg/kg IV over 90 minutes every 21 days for 3 cycles<br>* Other names: avastin;Drug: cisplatin<br>* Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles<br>Drug: gemcitabine hydrochloride<br>* Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles<br>Drug: paclitaxel<br>* After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles<br>Procedure: cysectomy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate |  | From day of first treatment until after cycle 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Survivin Levels |  | Baseline, week 6 and week 12 | 
| Urinary Cytogenitics |  | baseline and week 12 | 
| Progression Free Survival |  | from first treatment until time of progression or death, whichever comes first | 
| Median Overall Surivial |  | from first treatment until death | 
| Percentage of Planned Dose Received |  | from first treatment until end of week 12 | 
| Rate of Post-operative Complications |  | from first treatment until up to 48 hours after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transitional cell carcinoma of the bladder, stage III bladder cancer, stage II bladder cancer, recurrent bladder cancer