Two-Drug Combination Chemotherapy Compared With Four-Drug Combination Chemotherapy in Treating Patients With Advanced Cancer of the Urothelium

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003376

Collaborator

National Cancer Institute (NCI) (NIH), Cancer and Leukemia Group B (Other)

330

Enrollment

Locations

6.6

Patients Per Site

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 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 or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer	Drug: carboplatin Drug: cisplatin Drug: doxorubicin hydrochloride Drug: methotrexate Drug: paclitaxel Drug: vinblastine	Phase 3

Detailed Description

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 vs carboplatin and paclitaxel. II. Compare the relative toxic effects of these treatment regimens in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. 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. Treatment repeats every 28 days for a total of 6 courses in the absence of unacceptable toxicity or disease progression. Arm II: Patients receive paclitaxel IV over 3 hours immediately followed by carboplatin IV over 30 minutes. Treatment repeats every 21 days for a total of 6 courses in the absence of unacceptable toxicity 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Phase III Trial of Methotrexate, Vinblastine, Doxorubicin and Cisplatin vs Carboplatin and Paclitaxel in Advanced Carcinoma of the Urothelium

Study Start Date :

Sep 1, 1998

Actual Primary Completion Date :

Sep 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the urothelium (renal pelvis, ureter, bladder, or 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 significant pericardial or pleural effusion or edema No significant ascites No CNS metastases

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 Other: Prior malignancy allowed if curatively treated with no evidence of recurrence No active infection requiring parenteral antibiotics Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic biologic response modifier therapy No concurrent filgrastim (G-CSF) within 24 hours prior to and after study chemotherapy administration 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 No concurrent local radiotherapy for pain control or life-threatening situations Surgery: See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama	United States	35233
2	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
3	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
4	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
5	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
6	Lombardi Cancer Center, Georgetown University	Washington	District of Columbia	United States	20007
7	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
8	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
9	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois	United States	60612
10	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
11	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
12	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
13	Veterans Affairs Medical Center - Togus	Togus	Maine	United States	04330
14	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
15	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland	United States	21201
16	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
17	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
18	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
19	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
20	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
21	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
22	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
23	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
24	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
25	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
26	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
27	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
28	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
29	North Shore University Hospital	Manhasset	New York	United States	11030
30	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
31	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
32	Mount Sinai Medical Center, NY	New York	New York	United States	10029
33	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
34	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
35	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
36	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
37	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
38	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
39	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
40	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
41	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
42	Rhode Island Hospital	Providence	Rhode Island	United States	02903
43	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
44	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee	United States	38103
45	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
46	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont	United States	05201
47	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
48	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont	United States	05009
49	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
50	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037