Combination Chemotherapy in Treating Patients With Bladder Cancer

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003701

Collaborator

National Cancer Institute (NCI) (NIH)

490

Enrollment

Locations

99.5

Actual Duration (Months)

37.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 whether four-drug combination chemotherapy is more effective than two-drug combination chemotherapy in treating bladder cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Urethral Cancer	Drug: carboplatin Drug: cisplatin Drug: doxorubicin hydrochloride Drug: methotrexate Drug: paclitaxel Drug: vinblastine sulfate	Phase 3

Detailed Description

OBJECTIVES: I. Compare the recurrence rates and overall survival of patients treated with postoperative adjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) to those treated with combination paclitaxel and carboplatin for muscle invasive bladder cancer at particularly high risk of relapse. II. Compare the relative toxicities of postoperative M-VAC versus those encountered with postoperative paclitaxel and carboplatin. III. Compare the quality of life scores during and following completion of treatment of patients in these two treatment arms.

OUTLINE: This is a randomized study. Patients are stratified by N stage (N0 vs N+) and performance status (0-1 vs 2). Patients are randomized to receive methotrexate, vinblastine, doxorubicin, and cisplatin (arm I) or paclitaxel and carboplatin (arm II). Arm I: Patients receive methotrexate IV push on days 1, 15, and 22; vinblastine IV push on days 2, 15, and 22; doxorubicin IV push on day 2; and cisplatin IV over 2 hours on day 2. Treatment repeats every 28 days for 4 courses. Arm II: Patients receive paclitaxel IV over 3 hours on days 1 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Quality of life assessments are completed pretreatment, prior to course 3, 6 weeks after the last dose of chemotherapy, and at 6, 12, and 24 months from the end of therapy. Patients are followed every 3 months until year 2, every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 490 patients accrued into this study within 2.6 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

490 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase III Randomized Trial of Either M-VAC or Paclitaxel + Carboplatin as Postoperative Adjuvant Therapy in Patients With Muscle-Invasive Transitional Cell Carcinoma of the Bladder at High-Risk for Relapse

Actual Study Start Date :

Mar 1, 1999

Actual Primary Completion Date :

Aug 1, 2001

Actual Study Completion Date :

Jun 15, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the bladder or mixed histologies containing a component of transitional cell carcinoma Must have undergone radical cystectomy and pelvic lymph node dissection within 12 weeks prior to randomization No evidence of distant metastatic disease on pre- or postoperative radiographic scans No positive surgical margins in the cystectomy specimen and no known macroscopic residual disease left at time of cystectomy No bladder sparing surgery May have undergone continent urinary diversion or neobladder procedure but must have recovered completely from the effects of surgery Must have muscle-invasive disease on final pathologic staging and have a primary tumor stage of pT4, any N, M0, or any pT, N+, M0, or pT3b, any N, any M, and following a pelvic lymph node dissection have a pathologic nodal stage of pN0 (only if pT3b or pT4), pN1, or pN2 Clinically unsuspected organ confined prostate cancer found during cystoprostatectomy allowed

PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2 times ULN Renal: Creatinine no greater than 1.7 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No second degree atrioventricular block or bundle branch block Other: No history of prior malignancy in the past 5 years except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix No active infection requiring antibiotics No history of allergic reaction to drugs utilizing the vehicle Cremophor Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Recovered from all prior therapies Biologic therapy: No prior biologic response modifier therapy No filgrastim (G-CSF) 24 hours pre- or post-chemotherapy administration Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy as a component of bladder sparing therapy No prior adjuvant radiotherapy for locally advanced disease with positive margins Surgery: See Disease Characteristics Other: Prior intravesical therapy for superficial bladder cancer allowed and recovered

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
2	Indiana University Hospitals	Indianapolis	Indiana	United States	46202
3	Hunterdon Regional Cancer Center	Flemington	New Jersey	United States	08822
4	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
5	South Jersey Hospital - Millville	Millville	New Jersey	United States	08332
6	Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County	Mount Holly	New Jersey	United States	08060
7	Riverview Medical Center	Red Bank	New Jersey	United States	07701
8	Overlook Hospital	Summit	New Jersey	United States	07902-0220
9	Veterans Affairs Medical Center - New York	New York	New York	United States	10010
10	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
11	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
12	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19102-1192
13	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838