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


Phase 3
N/A
N/A
Open (Enrolling)
Both
Bladder Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Time to recurrence at 3 years

Safety Issue:

No

Principal Investigator

Richard J. Cote, MD, FRCPath

Investigator Role:

Study Chair

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000067639

NCT ID:

NCT00005047

Start Date:

September 1998

Completion Date:

Related Keywords:

  • Bladder Cancer
  • stage I bladder cancer
  • stage II bladder cancer
  • transitional cell carcinoma of the bladder
  • Urinary Bladder Neoplasms

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
CCOP - WichitaWichita, Kansas  67214-3882
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Veterans Affairs Medical Center - DaytonDayton, Ohio  45428
CCOP - DaytonKettering, Ohio  45429
CCOP - Western Regional, ArizonaPhoenix, Arizona  85006-2726
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
Veterans Affairs Medical Center - ShreveportShreveport, Louisiana  71130
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Veterans Affairs Medical Center - San Antonio (Murphy)San Antonio, Texas  78284
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Wilford Hall Medical CenterLackland Air Force Base, Texas  78236-5300
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Banner Good Samaritan Medical CenterPhoenix, Arizona  85006
Banner Thunderbird Medical CenterPhoenix, Arizona  85306
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Saint Anthony's Hospital at Saint Anthony's Health CenterAlton, Illinois  62002
Good Samaritan Regional Health CenterMt. Vernon, Illinois  62864
Cancer Center of Kansas, P.A. - El DoradoEl Dorado, Kansas  67042
Veterans Affairs Medical Center - Kansas CityKansas City, Kansas  64128
Southwest Medical CenterLiberal, Kansas  67901
Cancer Center of Kansas, P.A. - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, P.A. - WichitaWichita, Kansas  67214
William Beaumont Hospital - Royal Oak CampusRoyal Oak, Michigan  48073
St. Francis Medical CenterCape Girardeau, Missouri  63701
Southeast Missouri Regional Cancer Center at Southeast Missouri HospitalGape Girardeau, Missouri  63701
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Big Sky OncologyGreat Falls, Montana  59405
Sletten Regional Cancer InstituteGreat Falls, Montana  59405
St. Joseph Hospital Community Cancer CenterBellingham, Washington  98225
Olympic Hematology and OncologyBremerton, Washington  98310
Skagit Valley Hospital Cancer Care CenterMt. Vernon, Washington  98273
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Harborview Medical CenterSeattle, Washington  98104
Group Health Central HospitalSeattle, Washington  98104
North Puget Oncology at United General HospitalSedro-Wooley, Washington  98284
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Wenatchee Valley ClinicWenatchee, Washington  98801
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Cancer Center of Kansas, P.A. - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, P.A. - KingmanKingman, Kansas  67068
Cancer Center of Kansas, P.A. - NewtonNewton, Kansas  67114
Cancer Center of Kansas, P.A. - PrattPratt, Kansas  67124
Cancer Center of Kansas, P.A. - SalinaSalina, Kansas  67042
Salina Regional Health CenterSalina, Kansas  67401
Cancer Center of Kansas, P.A. - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, P.A. - Medical Arts TowerWichita, Kansas  67208
Associates in Womens Health, P.A. - North ReviewWichita, Kansas  67203
Cancer Center of Kansas, P.A. - WinfieldWinfield, Kansas  67156
Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveport, Louisiana  71130-3932
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Community Oncology Group at Cleveland Clinic Cancer CenterIndependence, Ohio  44131
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Middletown Regional HospitalMiddletown, Ohio  45044
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Cleveland Clinic - WoosterWooster, Ohio  44691
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Cancer Therapy and Research CenterSan Antonio, Texas  78229
University Hospital - San AntonioSan Antonio, Texas  78229
Community Comprehensive Cancer Center at Camden-Clark Memorial HospitalParkersburg, West Virginia  26102
Sentara Cancer Institute at Sentara Norfolk General HospitalNorfolk, Virginia  23507
Cancer Center of Kansas, P.A. - Dodge CityDodge City, Kansas  67801