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Combination Chemotherapy in Treating Patients With Bladder Cancer

Primary Purpose

Bladder Cancer, Urethral Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
carboplatin
cisplatin
doxorubicin hydrochloride
methotrexate
paclitaxel
vinblastine sulfate
Sponsored by
Eastern Cooperative Oncology Group
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring stage III bladder cancer, transitional cell carcinoma of the bladder, urethral cancer associated with invasive bladder cancer

Eligibility Criteria

0 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the bladder or mixed histologies containing a component of transitional cell carcinoma Must have undergone radical cystectomy and pelvic lymph node dissection within 12 weeks prior to randomization No evidence of distant metastatic disease on pre- or postoperative radiographic scans No positive surgical margins in the cystectomy specimen and no known macroscopic residual disease left at time of cystectomy No bladder sparing surgery May have undergone continent urinary diversion or neobladder procedure but must have recovered completely from the effects of surgery Must have muscle-invasive disease on final pathologic staging and have a primary tumor stage of pT4, any N, M0, or any pT, N+, M0, or pT3b, any N, any M, and following a pelvic lymph node dissection have a pathologic nodal stage of pN0 (only if pT3b or pT4), pN1, or pN2 Clinically unsuspected organ confined prostate cancer found during cystoprostatectomy allowed PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2 times ULN Renal: Creatinine no greater than 1.7 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No second degree atrioventricular block or bundle branch block Other: No history of prior malignancy in the past 5 years except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix No active infection requiring antibiotics No history of allergic reaction to drugs utilizing the vehicle Cremophor Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Recovered from all prior therapies Biologic therapy: No prior biologic response modifier therapy No filgrastim (G-CSF) 24 hours pre- or post-chemotherapy administration Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy as a component of bladder sparing therapy No prior adjuvant radiotherapy for locally advanced disease with positive margins Surgery: See Disease Characteristics Other: Prior intravesical therapy for superficial bladder cancer allowed and recovered

Sites / Locations

  • Veterans Affairs Medical Center - Atlanta (Decatur)
  • Indiana University Hospitals
  • Hunterdon Regional Cancer Center
  • Hackensack University Medical Center
  • South Jersey Hospital - Millville
  • Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County
  • Riverview Medical Center
  • Overlook Hospital
  • Veterans Affairs Medical Center - New York
  • NYU School of Medicine's Kaplan Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Center
  • Hahnemann University Hospital
  • Vanderbilt Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
June 13, 2023
Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003701
Brief Title
Combination Chemotherapy in Treating Patients With Bladder Cancer
Official Title
A Phase III Randomized Trial of Either M-VAC or Paclitaxel + Carboplatin as Postoperative Adjuvant Therapy in Patients With Muscle-Invasive Transitional Cell Carcinoma of the Bladder at High-Risk for Relapse
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 2, 1999 (Actual)
Primary Completion Date
August 2001 (Actual)
Study Completion Date
June 15, 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. 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 whether four-drug combination chemotherapy is more effective than two-drug combination chemotherapy in treating bladder cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have bladder cancer.
Detailed Description
OBJECTIVES: I. Compare the recurrence rates and overall survival of patients treated with postoperative adjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) to those treated with combination paclitaxel and carboplatin for muscle invasive bladder cancer at particularly high risk of relapse. II. Compare the relative toxicities of postoperative M-VAC versus those encountered with postoperative paclitaxel and carboplatin. III. Compare the quality of life scores during and following completion of treatment of patients in these two treatment arms. OUTLINE: This is a randomized study. Patients are stratified by N stage (N0 vs N+) and performance status (0-1 vs 2). Patients are randomized to receive methotrexate, vinblastine, doxorubicin, and cisplatin (arm I) or paclitaxel and carboplatin (arm II). Arm I: Patients receive methotrexate IV push on days 1, 15, and 22; vinblastine IV push on days 2, 15, and 22; doxorubicin IV push on day 2; and cisplatin IV over 2 hours on day 2. Treatment repeats every 28 days for 4 courses. Arm II: Patients receive paclitaxel IV over 3 hours on days 1 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Quality of life assessments are completed pretreatment, prior to course 3, 6 weeks after the last dose of chemotherapy, and at 6, 12, and 24 months from the end of therapy. Patients are followed every 3 months until year 2, every 6 months for years 2-5, and then annually thereafter. PROJECTED ACCRUAL: There will be 490 patients accrued into this study within 2.6 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Urethral Cancer
Keywords
stage III bladder cancer, transitional cell carcinoma of the bladder, urethral cancer associated with invasive bladder cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
490 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Type
Drug
Intervention Name(s)
vinblastine sulfate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the bladder or mixed histologies containing a component of transitional cell carcinoma Must have undergone radical cystectomy and pelvic lymph node dissection within 12 weeks prior to randomization No evidence of distant metastatic disease on pre- or postoperative radiographic scans No positive surgical margins in the cystectomy specimen and no known macroscopic residual disease left at time of cystectomy No bladder sparing surgery May have undergone continent urinary diversion or neobladder procedure but must have recovered completely from the effects of surgery Must have muscle-invasive disease on final pathologic staging and have a primary tumor stage of pT4, any N, M0, or any pT, N+, M0, or pT3b, any N, any M, and following a pelvic lymph node dissection have a pathologic nodal stage of pN0 (only if pT3b or pT4), pN1, or pN2 Clinically unsuspected organ confined prostate cancer found during cystoprostatectomy allowed PATIENT CHARACTERISTICS: Age: Any age Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2 times ULN Renal: Creatinine no greater than 1.7 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No second degree atrioventricular block or bundle branch block Other: No history of prior malignancy in the past 5 years except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix No active infection requiring antibiotics No history of allergic reaction to drugs utilizing the vehicle Cremophor Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Recovered from all prior therapies Biologic therapy: No prior biologic response modifier therapy No filgrastim (G-CSF) 24 hours pre- or post-chemotherapy administration Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy as a component of bladder sparing therapy No prior adjuvant radiotherapy for locally advanced disease with positive margins Surgery: See Disease Characteristics Other: Prior intravesical therapy for superficial bladder cancer allowed and recovered
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce J. Roth, MD
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Veterans Affairs Medical Center - Atlanta (Decatur)
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Indiana University Hospitals
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Hunterdon Regional Cancer Center
City
Flemington
State/Province
New Jersey
ZIP/Postal Code
08822
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
South Jersey Hospital - Millville
City
Millville
State/Province
New Jersey
ZIP/Postal Code
08332
Country
United States
Facility Name
Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County
City
Mount Holly
State/Province
New Jersey
ZIP/Postal Code
08060
Country
United States
Facility Name
Riverview Medical Center
City
Red Bank
State/Province
New Jersey
ZIP/Postal Code
07701
Country
United States
Facility Name
Overlook Hospital
City
Summit
State/Province
New Jersey
ZIP/Postal Code
07902-0220
Country
United States
Facility Name
Veterans Affairs Medical Center - New York
City
New York
State/Province
New York
ZIP/Postal Code
10010
Country
United States
Facility Name
NYU School of Medicine's Kaplan Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Hahnemann University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102-1192
Country
United States
Facility Name
Vanderbilt Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States

12. IPD Sharing Statement

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Combination Chemotherapy in Treating Patients With Bladder Cancer

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