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. It is not yet known if four-drug combination chemotherapy is more effective than two-drug combination chemotherapy in treating advanced cancer of the urothelium. PURPOSE: Randomized phase III trial to compare the effectiveness of four-drug combination chemotherapy with that of two-drug combination chemotherapy in treating patients who have advanced cancer of the urothelium.

Condition	Treatment or Intervention	Phase
stage III bladder cancer stage IV bladder cancer urethral cancer associated with invasive 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 anterior urethral cancer posterior urethral cancer	Drug: carboplatin  Drug: cisplatin  Drug: doxorubicin  Drug: methotrexate  Drug: paclitaxel  Drug: vinblastine	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the objective response rate, duration of remission, overall survival, and quality of life of patients with progressing regional or metastatic transitional cell carcinoma (or mixed histologies with a component of transitional cell carcinoma) of the urothelium treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) compared to carboplatin and paclitaxel. II. Compare the relative toxicities of M-VAC versus those encountered with carboplatin and paclitaxel in this patient population.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to receive either methotrexate, vinblastine, doxorubicin, and cisplatin (arm I) or paclitaxel and carboplatin (arm II). Arm I: Patients receive methotrexate IV on days 1, 15, and 22, vinblastine IV on days 2, 15, and 22, and cisplatin IV over 2 hours and doxorubicin IV on day 2. Courses repeat every 28 days. Arm II: Patients receive paclitaxel IV over 3 hours immediately followed by carboplatin IV over 30 minutes. Courses repeat every 21 days. Each treatment arm continues for a maximum of 6 courses in the absence of unacceptable toxic effects or disease progression. Quality of life is assessed before treatment, before courses 2 and 4, at 4 weeks after last course, and at 10 months. Patients are followed every 3 months for 1 year, and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study within 3.3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed transitional cell carcinoma of the urothelium (renal pelvis, ureter, bladder, urethra) or mixed histologies containing a component of transitional cell carcinoma of the urothelium with manifestations of progressing regional or metastatic cancer
• Clinically unsuspected organ confined prostate cancer found during cystoprostatectomy allowed
• Evaluable or measurable disease
• No CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: No prior systemic biologic response modifier therapy
• Chemotherapy: No prior systemic chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior pelvic radiotherapy as a component of bladder sparing therapy or as an adjuvant for locally advanced disease with positive margins
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: AST no greater than 2 times upper limit of normal; Bilirubin no greater than 1.5 mg/dL
• Renal: Creatinine no greater than 1.7 mg/dL
• Cardiovascular: No history of severe cardiovascular disease (American Heart Association class III or IV), uncontrolled congestive heart failure, or cardiac dysrhythmias; No significant pericardial effusion or edema
• Pulmonary: No significant pleural effusion or edema
• Other: No significant ascites; Prior malignancy allowed if curatively treated with no evidence of recurrence; No active infection requiring antibiotics; Not pregnant or nursing; Fertile patients must use effective contraception

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Lombardi Cancer Center, Georgetown University, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
      University of Illinois at Chicago Health Sciences Center, Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38103,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Vermont
      CCOP - Southwestern Vermont Regional Cancer Center, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States

Study chairs or principal investigators

Robert L. Comis,  Study Chair,  Eastern Cooperative Oncology Group   
Martin J. Edelman,  Study Chair

Study ID Numbers:  CDR0000066368; E-4897; GUMC-01011
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003376
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08