RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy following surgery in treating patients with advanced bladder cancer.

Condition	Treatment or Intervention	Phase
stage III bladder cancer stage IV bladder cancer metastatic transitional cell cancer of the renal pelvis and ureter regional transitional cell cancer of the renal pelvis and ureter transitional cell carcinoma of the bladder	Drug: cisplatin  Drug: doxorubicin  Drug: filgrastim  Drug: gemcitabine  Drug: paclitaxel	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity of sequential dose intensive adjuvant systemic therapy consisting of gemcitabine, then doxorubin, followed by paclitaxel and cisplatin with filgrastim (granulocyte colony stimulating factor; G-CSF) for patients with completely resected, locally advanced transitional cell carcinoma of the urothelium. II. Assess the disease free and overall survival of these patients.

PROTOCOL OUTLINE: Patients receive gemcitabine IV on weeks 1, 2, 3, 5, 6, and 7 for a total of 6 doses. A 1 week rest period occurs after the third dose of gemcitabine. At least 14 days after the last dose of gemcitabine, during the ninth week, patients receive doxorubicin at 2 week intervals (weeks 9, 11, 13, and 15) for a total of 4 doses. Filgrastim (granulocyte colony stimulating factor; G-CSF) is administered subcutaneously on days 3-10 of each cycle of doxorubicin. At least 14 days after the last dose of doxorubicin, during week 17, patients receive the combination of paclitaxel IV (3 hour infusion) and cisplatin, at 2 week intervals (weeks 17, 19, 21, and 23) for a total of 4 doses. G-CSF is again administered on days 3-10 of each of these cycles. Patients are followed every 3 months for the first 2 years, every 6 months for the next 3 years, then annually until death.

PROJECTED ACCRUAL: This study will accrue 25-30 patients in 1.5-2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically proven complete resection of locally advanced transitional cell carcinoma of the urothelium with negative margins; Disease extends beyond the bladder, the ureter, or into the regional lymph nodes; Stages eligible for patients with bladder cancer: Tany, N+, M0 T3b, N0, M0 T4a, N0, M0; Stages eligible for patients with urothelial cancer of the renal pelvis or ureter: Tany, N+, M0 T3, N0, M0 T4, N0, M0
• Local control of primary urothelial tumor obtained by: Cystoprostatectomy plus pelvic lymph node dissection for bladder cancer in males; Cystectomy/TAH/BSO and pelvic lymph node dissection for bladder cancer in females; Nephroureterectomy for disease involving the renal pelvis or ureter

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior systemic chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior irradiation of the bladder
• Surgery: See Disease Characteristics; Definitive surgery performed within 10 weeks of study treatment start

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%; ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Platelet count at least 150,000/mm3; Granulocyte count at least 1500/mm3
• Hepatic: Bilirubin less than 1.5 times normal; SGOT and alkaline phosphatase less than 2 times normal
• Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance at least 60 mL/ min
• Cardiovascular: LVEF at least 50%; No New York Heart Association class II or IV heart disease; No serious cardiac arrhythmias, including first, second, or third degree heart block
• Other: No concurrent second malignancy except nonmelanomatous skin cancer or curatively treated in situ carcinoma of the cervix; No uncontrolled infection; Fertile patients must use barrier method contraception before, during, and for 6 months after therapy and are encouraged to continue barrier method contraception for 2 years or longer

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Dean F. Bajorin,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000065899; MSKCC-97106; NCI-G97-1358
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003133
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08