Title
Cisplatin Plus Gemcitabine With or Without Paclitaxel in Treating Patients With Stage IV Urinary Tract Cancer
Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Cisplatin/Gemcitabine in Patients With Metastatic or Locally Advanced Urothelial Cancer Without Prior Systemic Therapy
Phase
Phase 3Study Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral CancerIntervention/Treatment
gemcitabine paclitaxel cisplatin ...Study Participants
608RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for urinary tract cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin plus gemcitabine with or without paclitaxel in treating patients who have stage IV urinary tract cancer.
OBJECTIVES:
Compare the duration of survival of patients with stage IV transitional cell carcinoma of the urothelium treated with cisplatin and gemcitabine with or without paclitaxel.
Compare the duration of progression-free survival, response rates, and duration of response in patients treated with these regimens.
Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, WHO performance status (0 vs 1), and presence of metastatic disease (yes vs no). Patients are randomized to one of two treatment arms.
Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and cisplatin IV over 1 hour on day 1 or 2. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive paclitaxel IV over 1 hour on days 1 and 8 followed by cisplatin IV over 1 hour on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for at least 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 610 patients (305 per treatment arm) will be accrued for this study within 3.04 years.
DISEASE CHARACTERISTICS: Histologically confirmed stage IV transitional cell carcinoma of the urothelium (pure or mixed) including bladder, urethra, ureter, and renal pelvis T4b, any N OR any T, N2-3 OR M1 Ineligible for surgery or radiotherapy with curative intent Measurable or evaluable disease No known CNS metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-1 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.25 times normal AST or ALT less than 2.5 times normal Renal: Glomerular filtration rate at least 60 mL/min Calcium normal or clinically insignificant Cardiovascular: No clinically significant cardiac arrhythmia No congestive heart failure No complete bundle branch block No New York Heart Association class III or IV heart disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation No psychological, familial, sociological, or geographical condition that would preclude study compliance No grade 3 or 4 infection without neutropenia No other serious concurrent systemic disorder that would preclude study therapy No mental disorder that would preclude study compliance No grade II or greater neuropathy No other prior or concurrent malignancy except appropriately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or incidental prostate cancer (T1, Gleason score no greater than 6, and PSA less than 0.5 ng/mL) PRIOR CONCURRENT THERAPY: Biologic therapy: No prior investigational biologic agents (e.g., antiangiogenic products, signal transduction pathway inhibitors, immunomodulators, or monoclonal antibody therapy) At least 4 weeks since prior immunotherapy Chemotherapy: No prior systemic chemotherapy At least 4 weeks since prior local intravesical chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No more than 1 prior course of radiotherapy At least 4 weeks since prior radiotherapy and recovered Surgery: See Disease Characteristics Prior urological procedures to relieve urinary tract obstruction and improve renal function allowed (e.g., ureteral stent or percutaneous nephrostomy)
