4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer

NCT00005047 | Terminated Phase 3 Results DMC

• 8 other identifiers: CDR0000067639LAC-USC-4B951SWOG-4B951NCI-G00-1715NYU-9852CAN-NCIC-BL10CCCWFU-88198U10CA032102
• Study Type: interventional
• Target: 521
• Locations: 2 countries
• Sites: 74

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 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.

Conditions

Bladder Cancer

Keywords

stage I bladder cancer; stage II bladder cancer; transitional cell carcinoma of the bladder

Outcome Measures

Primary Outcomes (1)

• Probability of Recurring

  p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Time from registration to the first observation of disease recurrence, censoring patients who died of unrelated causes. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.

  5 years

Secondary Outcomes (3)

• Probability of Overall Survival

  5 years

• Probability of Recurrence

  5 years

• Probability of Overall Survival

  5 years

Study Arms (4)

Arm I: M-VAC x 3

EXPERIMENTAL

Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC

Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: vinblastine

Arm II: Observation

NO INTERVENTION

Patients with altered (+) p53, reconsented to randomization, randomized to observation

Arm III: Observation

NO INTERVENTION

Patients with unaltered (-) p53

Arm IV: Observation

NO INTERVENTION

Patients with altered (+) p53, patients did not consent to randomization

Interventions

cisplatin DRUG

Arm I: M-VAC x 3

doxorubicin hydrochloride DRUG

Arm I: M-VAC x 3

methotrexate DRUG

Arm I: M-VAC x 3

vinblastine DRUG

Arm I: M-VAC x 3

Eligibility Criteria

• Age: Up to 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator
• NCIC Clinical Trials Group: collaborator
• University of Southern California: collaborator

Study Sites (74)

Banner Thunderbird Medical Center

Glendale, Arizona, 85306, United States

Location

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

CCOP - Western Regional, Arizona

Phoenix, Arizona, 85006, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, 62002, United States

Location

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Good Samaritan Regional Health Center

Mount Vernon, Illinois, 62864, United States

Location

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, 46107, United States

Location

Cancer Center of Kansas, P.A. - Chanute

Chanute, Kansas, 66720, United States

Location

Cancer Center of Kansas, P.A. - Dodge City

Dodge City, Kansas, 67801, United States

Location

Cancer Center of Kansas, P.A. - El Dorado

El Dorado, Kansas, 67042, United States

Location

Veterans Affairs Medical Center - Kansas City

Kansas City, Kansas, 64128, United States

Location

Cancer Center of Kansas, P.A. - Kingman

Kingman, Kansas, 67068, United States

Location

Southwest Medical Center

Liberal, Kansas, 67901, United States

Location

Cancer Center of Kansas, P.A. - Newton

Newton, Kansas, 67114, United States

Location

Cancer Center of Kansas, P.A. - Parsons

Parsons, Kansas, 67357, United States

Location

Cancer Center of Kansas, P.A. - Pratt

Pratt, Kansas, 67124, United States

Location

Cancer Center of Kansas, P.A. - Salina

Salina, Kansas, 67042, United States

Location

Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

Cancer Center of Kansas, P.A. - Wellington

Wellington, Kansas, 67152, United States

Location

Associates in Womens Health, P.A. - North Review

Wichita, Kansas, 67203, United States

Location

Cancer Center of Kansas, P.A. - Medical Arts Tower

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas, P.A. - Wichita

Wichita, Kansas, 67214, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214, United States

Location

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Cancer Center of Kansas, P.A. - Winfield

Winfield, Kansas, 67156, United States

Location

Veterans Affairs Medical Center - Shreveport

Shreveport, Louisiana, 71101, United States

Location

Feist-Weiller Cancer Center at Louisiana State University Health Sciences

Shreveport, Louisiana, 71130-3932, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, 48073, United States

Location

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

Cape Girardeau, Missouri, 63701, United States

Location

St. Francis Medical Center

Cape Girardeau, Missouri, 63701, United States

Location

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, 63141, United States

Location

David C. Pratt Cancer Center at St. John's Mercy

St Louis, Missouri, 63141, United States

Location

Big Sky Oncology

Great Falls, Montana, 59405, United States

Location

Sletten Regional Cancer Institute

Great Falls, Montana, 59405, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital

Dayton, Ohio, 45406, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Cancer Care Center

Dayton, Ohio, 45415, United States

Location

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, 45428, United States

Location

CCOP - Dayton

Dayton, Ohio, 45429, United States

Location

Community Oncology Group at Cleveland Clinic Cancer Center

Independence, Ohio, 44131, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

Middletown Regional Hospital

Middletown, Ohio, 45044, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

Cleveland Clinic - Wooster

Wooster, Ohio, 44691, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Wilford Hall Medical Center

Lackland Air Force Base, Texas, 78236, United States

Location

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, 78209, United States

Location

Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

University Hospital - San Antonio

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

Sentara Cancer Institute at Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

St. Joseph Hospital Community Cancer Center

Bellingham, Washington, 98225, United States

Location

Olympic Hematology and Oncology

Bremerton, Washington, 98310, United States

Location

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, 98273, United States

Location

CCOP - Virginia Mason Research Center

Seattle, Washington, 98101, United States

Location

Group Health Central Hospital

Seattle, Washington, 98104, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, 98114, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195-6043, United States

Location

North Puget Oncology at United General Hospital

Sedro-Woolley, Washington, 98284, United States

Location

Cancer Care Northwest - Spokane South

Spokane, Washington, 99202, United States

Location

Wenatchee Valley Clinic

Wenatchee, Washington, 98801, United States

Location

Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital

Parkersburg, West Virginia, 26102, United States

Location

Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

• von Rundstedt FC, Mata DA, Groshen S, Stein JP, Skinner DG, Stadler WM, Cote RJ, Kryvenko ON, Godoy G, Lerner SP. Significance of lymphovascular invasion in organ-confined, node-negative urothelial cancer of the bladder: data from the prospective p53-MVAC trial. BJU Int. 2015 Jul;116(1):44-9. doi: 10.1111/bju.12997. Epub 2015 Mar 25.

  PMID: 25413313 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; Doxorubicin; Methotrexate; Vinblastine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Susan Groshen
• Organization: University of Southern California

Susan.Groshen@med.usc.edu

323-865-0375

Study Officials

• Richard J. Cote, MD, FRCPath

  University of Southern California

  STUDY CHAIR

• Laurence H. Klotz, MD

  Toronto Sunnybrook Regional Cancer Centre

  STUDY CHAIR

• Seth P Lerner, MD

  Baylor College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2000
• First Posted: January 27, 2003
• Study Start: August 1, 1997
• Primary Completion: March 1, 2011
• Study Completion: December 1, 2014
• Last Updated: June 8, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-05

Locations

CA (1); US (73)