Bladder Cancer
Conditions
Keywords
transitional cell carcinoma of the bladder, stage III bladder cancer, stage II bladder cancer, recurrent bladder cancer
Brief 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.
Interventions
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
Sponsors
Study design
Eligibility
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Remission Rate | From day of first treatment until after cycle 3 |
Secondary
| Measure | Time frame |
|---|---|
| Urinary Cytogenitics | baseline and week 12 |
| Progression Free Survival | from first treatment until time of progression or death, whichever comes first |
| Urinary Survivin Levels | Baseline, week 6 and week 12 |
| 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. |
| Median Overall Surivial | from first treatment until death |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Intervention 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.
bevacizumab: 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
cisplatin: Before surgery: given as a 70mg/m2 IV over 60 minutes every 21 days for 4 cycles
gemcitabine hydrochloride: Before surgery: given as a 1000mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle for 4 cycles
paclitaxel: After surgery: given as a 175 mg/m2 dose ver 3 hours every 21 days for 3 cycles
cysectomy | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Study Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Complete Remission Rate
Time frame: From day of first treatment until after cycle 3
Population: Data for this outcome measure was not collected
Median Overall Surivial
Time frame: from first treatment until death
Population: Data for this outcome measure was not collected
Percentage of Planned Dose Received
Time frame: from first treatment until end of week 12
Population: Data for this outcome measure was not collected
Progression Free Survival
Time frame: from first treatment until time of progression or death, whichever comes first
Population: Data for this outcome measure was not collected
Rate of Post-operative Complications
Time frame: from first treatment until up to 48 hours after surgery.
Population: Data for this outcome measure was not collected
Urinary Cytogenitics
Time frame: baseline and week 12
Population: Data for this outcome measure was not collected
Urinary Survivin Levels
Time frame: Baseline, week 6 and week 12
Population: Data for this outcome measure was not collected