S0219, Combination Chemotherapy Followed By Observation or Surgery in Patients With Stage II or Stage III Cancer of the Urothelium
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 and decrease the need for surgery.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium.
Transitional Cell Cancer of the Renal Pelvis and Ureter
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Sequential Approach to the Treatment of Muscle Invasive, Non-Metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant Gemcitabine, Paclitaxel and Carboplatin With Molecular Correlates|
- Pathologic complete response rate by transurethral resection of bladder tumor (TURBT) and imaging studies after chemotherapy [ Time Frame: assessed at end-of-study cystectomy ] [ Designated as safety issue: No ]
- Molecular markers predicting response and survival [ Time Frame: end of year 5 ] [ Designated as safety issue: No ]
- Evaluate recurrence rates and cystectomy-free survival [ Time Frame: every 6 months for 2 years, then annually for 5 years ] [ Designated as safety issue: No ]
- Evaluate survival [ Time Frame: every 6 months for 2 years, then annually for 5 years ] [ Designated as safety issue: No ]
- Assess toxicities [ Time Frame: weeks 1, 2, 4, 5, 7, 8, and following surgery ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2003|
|Study Completion Date:||December 2011|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine, Paclitaxel, Carboplatin
Gemcitabine, Paclitaxel, Carboplatin followed by surgery
Other Name: gemcitabine hydrochlorideDrug: paclitaxel
Other Name: TaxolProcedure: surgery
- Determine the pathologic complete response of patients with stage II or III transitional cell cancer of the urothelium treated with neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by observation or immediate cystectomy.
- Determine, preliminarily, if molecular markers predict response, survival, and tumor recurrence in patients treated with these regimens.
- Determine recurrence rates and cystectomy-free survival of patients who choose observation after an initial response to neoadjuvant chemotherapy.
- Compare the survival of patients treated with neoadjuvant chemotherapy followed by cystectomy vs observation.
- Determine the feasibility, tolerability, and toxicity of these regimens in these patients.
OUTLINE: This is a multicenter study.
Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Within 4-8 weeks after completion of neoadjuvant chemotherapy, patients undergo a third transurethral resection of bladder tumor.
Patients with T0 disease after neoadjuvant chemotherapy may choose to undergo observation. These patients undergo cystoscopies with biopsies every 3 months for 1 year, every 4 months for 1 year, and then every 6 months until disease progression.
Patients with T1 disease or greater after neoadjuvant chemotherapy undergo immediate cystectomy. Patients with T0 disease may also choose this option. Patients undergoing immediate cystectomy are followed every 6 months for 2 years and then annually for 3 years.
PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study within 2 years.