Combination Chemotherapy in Treating Patients With Bladder Cancer - Full Text View

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI) National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00005047

Purpose

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.

Condition	Intervention	Phase
Bladder Cancer	Drug: cisplatin Drug: doxorubicin hydrochloride Drug: methotrexate Drug: vinblastine Procedure: adjuvant therapy	Phase III

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Methotrexate Cisplatin Doxorubicin Doxorubicin hydrochloride Myocet Vinblastine sulfate Vinblastine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) in Organ-Confined Bladder Cancer Based on p53 Status

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Time to recurrence at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival at 3 years [ Designated as safety issue: No ]

Study Start Date:

September 1998

Detailed 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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005047

Show 74 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

National Cancer Institute of Canada

Investigators

Study Chair:	Richard J. Cote, MD, FRCPath	Norris Comprehensive Cancer Center
Study Chair:	Laurence H. Klotz, MD	Edmond Odette Cancer Centre at Sunnybrook

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000067639, SWOG-4B951, LAC-USC-4B951, NCI-G00-1715, NYU-9852, CAN-NCIC-BL10, CCCWFU-88198
Study First Received:	April 6, 2000
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00005047 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Antimetabolites
Urinary Tract Neoplasm
Immunologic Factors
Urogenital Neoplasms
Vinblastine
Urologic Neoplasms
Carcinoma, Transitional Cell
Anti-Bacterial Agents
Urologic Diseases
Cisplatin
Methotrexate
Bladder Neoplasm
Cystocele
Urinary Bladder Diseases

Urinary Bladder Neoplasms
Adjuvants, Immunologic
Antimitotic Agents
Folic Acid Antagonists
Immunosuppressive Agents
Doxorubicin
Carcinoma
Folic Acid
Radiation-Sensitizing Agents
Tubulin Modulators
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Transitional Cell Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Vinblastine
Urogenital Neoplasms
Reproductive Control Agents
Urologic Neoplasms
Antibiotics, Antineoplastic
Neoplasms by Site
Cisplatin
Urologic Diseases
Therapeutic Uses

Abortifacient Agents
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Mitosis Modulators
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009