4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer

Bladder Cancer Clinical Trial

Official title:

MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) in Organ-Confined Bladder Cancer Based on p53 Status

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00005047
• Other study ID #: CDR0000067639
• Secondary ID: LAC-USC-4B951SWO
• Status: Active, not recruiting
• Phase: Phase 3
• First received: April 6, 2000
• Last updated: July 21, 2011
• Start date: September 1998

Study information

• Verified date: June 2011
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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 combination chemotherapy is more effective than observation alone in treating bladder cancer.

PURPOSE: This randomized phase III trial is studying combination chemotherapy to see how well it works compared to observation alone in treating patients with bladder cancer.

Description:

OBJECTIVES:

• Compare the recurrence-free and overall survival in patients with transitional cell carcinoma of the bladder with p53 gene alterations treated with methotrexate, vinblastine, doxorubicin, and cisplatin vs observation alone.

• Compare the recurrence-free and overall survival in patients with or without p53 gene alterations treated with observation alone.

• Examine the expression of p53 and other genes, particularly RB, p21, and p16, involved in cell cycle regulation that may be involved in the response to chemotherapy in these patients.

• Correlate p53 mutational gene status with p53 protein expression by immunohistochemistry, outcome (recurrence-free and overall survival), response to chemotherapy, and expression of key molecules in the p53-mediated apoptotic pathway in patients treated with this regimen vs observation alone.

OUTLINE: This is a randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups based on the status of the p53 gene in the bladder tumor.

• Group A (p53 gene alteration, defined by greater than 10% nuclear reactivity): Patients are stratified according to age (under 65 vs 65 and over), stage (P1 vs P2a vs P2b), grade (1 or 2 vs 3 or 4), and p21 status. Patients are randomized to 1 of 2 treatment arms within 10 weeks after radical cystectomy and bilateral pelvic lymphadenectomy and within 2 weeks after registration.

• Arm I: Within 2 weeks after randomization, patients receive methotrexate IV on days 1, 15, and 22; vinblastine IV on days 2, 15, and 22; and doxorubicin IV and cisplatin IV on day 2. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation for recurrence but do not receive adjuvant chemotherapy after surgery.

Patients who are eligible for randomization but decline to be randomized undergo observation for recurrence.

• Group B (p53 gene normal, defined by less than 10% nuclear reactivity): Patients undergo observation for recurrence but do not receive adjuvant chemotherapy after surgery.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study within 4.75 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 800
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven organ confined transitional cell carcinoma (TCC) of the bladder

• Must have undergone radical cystectomy and bilateral pelvic lymphadenectomy with pathologic stage from definitive cystectomy specimen of P1, P2a, or P2b and N0, M0 TCC with or without squamous/glandular differentiation (no adenocarcinoma, squamous cell carcinoma, or small cell carcinoma)

• Margins must be negative for invasive or in situ TCC

• In situ TCC in the urethra or ureter(s) allowed provided margins are negative

• Clinical stage T1, T2a, or T2b based on transurethral resection bladder tumor specimen with P0 or PIS and N0, M0 TCC allowed

• Incidental pT2a (Gleason score no greater than 7), pT2b (Gleason score no greater than 7), or pT2c (Gleason score no greater than 7) adenocarcinoma of the prostate allowed

• No invasive tumor into ureter(s) or urethra

• Must have potentially curable disease

• Must register within 9 weeks after surgery

• No metastatic disease by physical exam and chest x-ray or CT scan of the chest

• Eligible for randomization if:

• p53 gene alteration present

• Randomization occurs within 10 weeks after surgery

• Those who are randomized to receive (MVAC) methotrexate, vinblastine, doxorubicin, and cisplatin begin MVAC within 12 weeks after cystectomy

• No metastatic disease by physical exam and chest x-ray or CT scan of the chest

• No prohibitive medical risk for chemotherapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• ECOG 0-1 OR

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 4,000/mm^3

• Platelet count at least 150,000/mm^3

Hepatic

• SGOT or SGPT no greater than 2 times normal

• Alkaline phosphatase no greater than 2 times normal

• Bilirubin normal

Renal

• Creatinine no greater than 1.8 mg/dL OR

• Creatinine clearance at least 50 mL/min

• Blood urea nitrogen normal

Cardiovascular

• No serious arrhythmias

• No congestive heart disease with New York Heart Association class III or IV status

• Randomization group:

• Ejection fraction must be at least 50% by MUGA scan if there is a clinical concern regarding the patient's cardiac status

Other

• No other malignancy (including synchronous papillary or invasive upper urinary tract malignancy) within the past 5 years except incidental prostate cancer (found at cystectomy), basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix

• No concurrent advanced medical illness or psychologic disease

• No prohibitive medical risk for chemotherapy

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

• No prior systemic chemotherapy for bladder cancer

• At least 5 years since other prior systemic chemotherapy

• Prior intravesical therapy allowed

• Randomization group:

• Prior intravesical therapy allowed if administered prior to cystectomy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic irradiation

Surgery

• See Disease Characteristics

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin

• doxorubicin hydrochloride

• methotrexate

• vinblastine

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Canada	Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre	Toronto	Ontario
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. Francis Medical Center	Cape Girardeau	Missouri
United States	Cancer Center of Kansas, P.A. - Chanute	Chanute	Kansas
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Cancer Center of Kansas, P.A. - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, P.A. - El Dorado	El Dorado	Kansas
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri
United States	Banner Thunderbird Medical Center	Glendale	Arizona
United States	Big Sky Oncology	Great Falls	Montana
United States	Sletten Regional Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, P.A. - Kingman	Kingman	Kansas
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Southwest Medical Center	Liberal	Kansas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Good Samaritan Regional Health Center	Mt. Vernon	Illinois
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Cancer Center of Kansas, P.A. - Newton	Newton	Kansas
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	Cancer Center of Kansas, P.A. - Parsons	Parsons	Kansas
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	Cancer Center of Kansas, P.A. - Pratt	Pratt	Kansas
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Cancer Center of Kansas, P.A. - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Cancer Therapy and Research Center	San Antonio	Texas
United States	University Hospital - San Antonio	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Cancer Center of Kansas, P.A. - Wellington	Wellington	Kansas
United States	Wenatchee Valley Clinic	Wenatchee	Washington
United States	Associates in Womens Health, P.A. - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Winfield	Winfield	Kansas
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Southwest Oncology Group	Canadian Cancer Trials Group, National Cancer Institute (NCI), University of Southern California

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to recurrence at 3 years			No
Secondary	Overall survival at 3 years			No