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.

Condition	Treatment or Intervention	Phase
Bladder Cancer transitional cell cancer of the renal pelvis and ureter Urethral Cancer	Drug: carboplatin  Drug: gemcitabine  Drug: paclitaxel  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed muscle-invasive (T2-T4a), node-negative (N0) transitional cell cancer (TCC) of the urothelium (bladder, renal pelvis, ureter, or urethra)
• No adenocarcinoma, small cell carcinoma, sarcomas, squamous cell carcinoma, or mixed histology
• Disease diagnosed with an initial transurethral resection of bladder tumor (TURBT) and a second TURBT performed within 8 weeks of first with attempt to remove all tumor present
• Residual disease after second TURBT allowed
• No more than 14-56 days after second TURBT
• No metastatic disease by chest x-ray and CT scan or MRI of the abdomen and pelvis
• Fresh tumor tissue, paraffin tumor tissue, unstained slides, or cell block specimen from one or both TURBTs available

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,500/mm^3
• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least lower limit of normal

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL AND/OR
• Creatinine clearance at least 60 mL/min

Other

• No prohibitive medical risk that would preclude radical cystectomy
• No other serious concurrent systemic disorder that would preclude study compliance
• No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease-free for 5 years
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior intravesical immunotherapy allowed

Chemotherapy

• No prior systemic chemotherapy for TCC of the urothelium
• Prior intravesical chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for TCC of the urothelium
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States; Recruiting
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States; Recruiting
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States; Recruiting
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States; Recruiting
      Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange,  California,  92868,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7390,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States; Recruiting
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States; Recruiting
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States; Recruiting
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
      Providence Cancer Institute at Providence Hospital - Southfield, Southfield,  Michigan,  48075,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0946,  United States; Recruiting
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States; Recruiting
      Saint Louis University Cancer Center, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
      Western New York Urology Associates, Buffalo,  New York,  14220,  United States; Recruiting
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States; Recruiting
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States; Recruiting
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4095,  United States; Recruiting
      Southwest Cancer and Research Center at University Medical Center, Lubbock,  Texas,  79415-3364,  United States; Recruiting
      Texas Tech University Health Sciences Center School of Medicine, Amarillo,  Texas,  79106,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States; Recruiting
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States; Recruiting
Virginia
      Sentara Cancer Institute at Sentara Norfolk General Hospital, Norfolk,  Virginia,  23510-1115,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States; Recruiting
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States; Recruiting
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States; Recruiting

Study chairs or principal investigators

Primo N. Lara, MD,  Study Chair,  University of California Davis Cancer Center   

Study ID Numbers:  CDR0000256921; SWOG-S0219; NCT00045630
Record last reviewed:  October 2004
Last Updated:  April 4, 2005
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045630
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08