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
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: bevacizumab; cisplatin; gemcitabine hydrochloride; paclitaxel; cysectomy
Intervention description: 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; Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles; Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles; After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles
Intervention MeSH terms: Paclitaxel; Bevacizumab; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: transitional cell carcinoma of the bladder; stage III bladder cancer; stage II bladder cancer; recurrent bladder cancer

Summary:

      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.
    

Eligibility criteria:

        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