Comparison of Immediate and Delayed Adjuvant Chemotherapy in Treating Patients Who Have Undergone a Radical Cystectomy for Stage III or Stage IV Transitional Cell Carcinoma of the Bladder Urothelium - Full Text View

Sponsors and Collaborators:	European Organization for Research and Treatment of Cancer National Cancer Institute (NCI) Groupe D'Etude des Tumeurs Uro-Genitales Nordic Urothelial Cancer Group National Cancer Institute of Canada Institute of Cancer Research, United Kingdom American College of Surgeons
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00028756

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 and giving them after surgery may kill any remaining tumor cells. It is not yet known if adjuvant chemotherapy is more effective when given immediately after radical cystectomy (surgery to remove the bladder) or when the cancer returns.

PURPOSE: Randomized phase III trial to compare the effectiveness of immediate adjuvant chemotherapy with that of adjuvant chemotherapy given when the cancer returns in treating patients who have undergone a radical cystectomy for stage III or stage IV transitional cell carcinoma of the bladder urothelium.

Condition	Intervention	Phase
Bladder Cancer	Drug: cisplatin Drug: doxorubicin hydrochloride Drug: filgrastim Drug: gemcitabine 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: Doxorubicin Doxorubicin hydrochloride Filgrastim Methotrexate Cisplatin Gemcitabine hydrochloride Gemcitabine Vinblastine Vinblastine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase III Trial Comparing Immediate Versus Deferred Chemotherapy After Radical Cystectomy in Patients With pT3-pT4, and/or N+MO Transitional Cell Carcinoma (TCC) of the Bladder

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

Primary Outcome Measures:

Duration of survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	660
Study Start Date:	October 2001
Estimated Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the overall and progression-free survival of patients with stage III or IV transitional cell carcinoma of the bladder urothelium treated with immediate versus deferred adjuvant chemotherapy after radical cystectomy.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, tumor status (pT1-2 vs pT3 vs pT4), and node status (node positive vs node negative with 15 or more nodes sampled vs node negative with less than 15 nodes sampled). Patients are randomized to one of two treatment arms.

Arm I: Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy.
Arm II: Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy.

Patients in both arms receive one of the following chemotherapy regimens to be determined by participating center:

Regimen A (Classical M-VAC): Patients receive classical M-VAC comprising 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. Courses repeat every 28 days.
Regimen B (High-dose M-VAC): Patients receive high-dose M-VAC comprising methotrexate IV on day 1 and vinblastine IV, doxorubicin IV, and cisplatin IV on day 2. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-10. Courses repeat every 14 days.
Regimen C (Gemcitabine and cisplatin): Patients receive gemcitabine and cisplatin comprising gemcitabine IV over 30 minutes on days 1, 8, and 15 followed by cisplatin IV on day 1 or 2. Courses repeat every 28 days.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 660 will be accrued for this study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed transitional cell carcinoma of the bladder urothelium
- T3-4, N1-3, M0
No pure squamous cell or adenocarcinoma tumors
No more than 90 days since prior radical cystectomy and bilateral lymphadenectomy without evidence of microscopic residual disease

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

WHO 0-1

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,500/mm^3
Platelet count at least 120,000/mm^3

Hepatic:

SGOT/SGPT less than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase less than 2.5 times ULN
Bilirubin normal

Renal:

Glomerular filtration rate greater than 60 mL/min

Cardiovascular:

No clinically significant cardiac arrhythmia
No congestive heart failure
No complete bundle branch block
No New York Heart Association class III or IV heart disease

Other:

Not pregnant or nursing
Fertile patients must use effective contraception during and for 6 months after study
Considered fit for cisplatin-containing combination chemotherapy
No clinically abnormal auditory function
No known hypersensitivity to E. coli-derived drug preparations
No grade 2 or greater peripheral neuropathy
No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix, treated basal cell skin cancer, or treated incidental prostate cancer (pT2, Gleason score no greater than 6, and PSA less than 0.5 ng/mL)
No psychological, familial, sociological, or geographical condition that would preclude study involvement

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior systemic chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy to the bladder

Surgery:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028756

Show 106 Study Locations

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

National Cancer Institute (NCI)

Groupe D'Etude des Tumeurs Uro-Genitales

Nordic Urothelial Cancer Group

National Cancer Institute of Canada

Institute of Cancer Research, United Kingdom

American College of Surgeons

Investigators

Investigator:	Cora N. Sternberg, MD, FACP	Vincenzo Pansadoro Foundation
Study Chair:	Christine Theodore, MD	Institut Gustave Roussy
Study Chair:	Sten Nilsson, MD	Karolinska University Hospital - Solna
Study Chair:	Armen G. Aprikian, MD	Montreal General Hospital
Study Chair:	Michael Leahy, MBChB, FRACP, FRCP, FRC Path	Fremantle Hospital
Study Chair:	Ian Tannock, MD, PhD	Princess Margaret Hospital, Canada

More Information

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

Study ID Numbers:	CDR0000069130, EORTC-30994, ACOSOG-EORTC-30994, CAN-NCIC-EORTC-30994, FNCLCC-GETUG-EORTC-30994, JUG-EORTC-30994, NORDIC-EORTC-30994, SEUG-EORTC-30994, SWOG-EORTC-30994, UKCCCR-EORTC-30994, NCRI-BLADDER-EORTC-30994
Study First Received:	January 4, 2002
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00028756
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage III bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder

Study placed in the following topic categories:

Cystocele
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Vinblastine
Urogenital Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Transitional cell carcinoma
Doxorubicin

Carcinoma
Folic Acid
Cisplatin
Urologic Diseases
Methotrexate
Gemcitabine
Urinary tract neoplasm
Neoplasms, Glandular and Epithelial
Bladder neoplasm

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Abortifacient Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

Neoplasms by Histologic Type
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009