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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

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ClinicalTrials.gov Identifier: NCT00028756
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : August 2, 2016
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Groupe D'Etude des Tumeurs Uro-Genitales
Institute of Cancer Research, United Kingdom
NCIC Clinical Trials Group
Arbeitsgemeinschaft Urologische Onkologie
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:
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. 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.

Condition or disease Intervention/treatment Phase
Stage III Bladder Cancer Stage IV Bladder Cancer Transitional Cell Carcinoma of the Bladder Drug: doxorubicin hydrochloride Drug: gemcitabine hydrochloride Drug: vinblastine sulfate Drug: methotrexate Drug: cisplatin Biological: filgrastim Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. 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 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 and EORTC.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 285 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial Comparing Immediate Versus Deferred Chemotherapy After Radical Cystectomy in Patients With pT3-pT4, and/or N+M0 Transitional Cell Carcinoma (TCC) of the Bladder
Study Start Date : October 2001
Actual Primary Completion Date : January 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Active Comparator: Arm I (immediate chemotherapy)
Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

Drug: vinblastine sulfate
Given IV
Other Names:
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar

Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen

Experimental: Arm II (deferred chemotherapy)
Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

Drug: vinblastine sulfate
Given IV
Other Names:
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar

Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen




Primary Outcome Measures :
  1. Duration of survival [ Time Frame: 5 years ]
    Estimated using the Kaplan-Meier technique and compared based on a two sided logrank test with retrospective stratification for the participating cooperative group, the chemotherapy regimen, the T category and the nodal status.

  2. Duration of progression-free survival [ Time Frame: 5 years ]
    Estimated using the Kaplan-Meier technique and compared based on a two sided logrank test with retrospective stratification for the participating cooperative group, the chemotherapy regimen, the T category and the nodal status.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Performance status - WHO 0-1
  • WBC at least 3,500/mm^3
  • Platelet count at least 120,000/mm^3
  • SGOT/SGPT less than 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 2.5 times ULN
  • Bilirubin normal
  • Glomerular filtration rate greater than 60 mL/min
  • 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
  • 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
  • No prior systemic chemotherapy
  • No prior radiotherapy to the bladder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00028756


Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
National Cancer Institute (NCI)
Groupe D'Etude des Tumeurs Uro-Genitales
Institute of Cancer Research, United Kingdom
NCIC Clinical Trials Group
Arbeitsgemeinschaft Urologische Onkologie
Investigators
Study Chair: Cora Sternberg, Dr. San Camillo Forlanini Hospitals

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00028756     History of Changes
Other Study ID Numbers: EORTC 30994
EORTC-30994
CDR0000069130
CAN-NCIC-EORTC-30994
ACOSOG-EORTC-30994
NCRI-BLADDER-EORTC-30994
UKCCCR-EORTC-30994
FNCLCC-GETUG-EORTC-30994
N02CM62212 ( Other Grant/Funding Number: US NIH Grant/Contract Award Number )
2005-003741-13 ( EudraCT Number )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: August 2, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Methotrexate
Doxorubicin
Liposomal doxorubicin
Vinblastine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Abortifacient Agents, Nonsteroidal