Title
Cisplatin and Gemcitabine Compared With Observation in Treating Patients Who Have Undergone Surgery for Bladder Cancer
Phase III Study Of Adjuvant Cisplatin-Gemcitabine Vs. Observation After Radical Cystectomy In High-Risk Bladder Cancer
Phase
Phase 3Lead Sponsor
Fondazione Toscana Gabriele MonasterioStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Bladder CancerIntervention/Treatment
gemcitabine cisplatin ...Study Participants
700RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy is effective in preventing relapse in patients who have undergone radical cystectomy for bladder cancer.
PURPOSE: Phase III trial to compare the effectiveness of cisplatin combined with gemcitabine with that of observation in treating patients with bladder cancer who have undergone surgery to remove the bladder.
OBJECTIVES:
Compare the overall, cause-specific, and disease-free survival of patients with high-risk muscle-invasive transitional cell carcinoma of the bladder treated with adjuvant cisplatin and gemcitabine vs observation after radical cystectomy.
Compare the dose intensity and toxicity of two different schedules of cisplatin and gemcitabine in these patients.
Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and disease status (T2 [G3 only] or T3-4 [any G], N0-2 vs any T, N1-2, M0). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients are further randomized to 1 of 2 treatment regimens.
Regimen A: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15.
Regimen B: Patients receive cisplatin IV on day 15 and gemcitabine as in regimen A.
Treatment in both regimens repeats every 28 days for 4 courses.
Arm II: Patients undergo observation followed by cisplatin and gemcitabine as in arm I at relapse.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.
DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the bladder T2 (G3 only) or T3-4 (any G), N0-2 or any T, N1-2, M0 No secondary localization Radical cystectomy (without residual disease) performed within 10 weeks prior to study entry to include: Men: Cystectomy with removal of prostate and seminal vesicles including 1.5 cm of urethra plus pelvic lymphadenectomy (at least 15 negative lymph nodes are recommended to define as N0) Women: Cystectomy with complete removal of the bladder, uterus, ovaries, and anterior walls of the vagina plus pelvic lymphadenectomy PATIENT CHARACTERISTICS: Age 18 to 74 Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC at least 3,500/mm^3 Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Bilirubin less than upper normal limit (ULN) Gamma-GT less than ULN SGOT and SGPT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal Creatinine no greater than1.25 times ULN Creatinine clearance at least 60 mL/min Cardiovascular No congestive heart failure No angina pectoris No cardiac arrhythmia No uncontrolled arterial hypertension No history of acute myocardial infarction within the past year Other No other serious concurrent illness PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior systemic chemotherapy Endocrine therapy Not specified Radiotherapy Palliative radiotherapy allowed at relapse for symptomatic bone metastases Surgery See Disease Characteristics
