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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

Tracking Information
First Submitted Date  ICMJE January 4, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date August 2, 2016
Study Start Date  ICMJE October 2001
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2013)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Stage III Bladder Cancer
  • Stage IV Bladder Cancer
  • Transitional Cell Carcinoma of the Bladder
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Arm I (immediate chemotherapy)
    Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: gemcitabine hydrochloride
    • Drug: vinblastine sulfate
    • Drug: methotrexate
    • Drug: cisplatin
    • Biological: filgrastim
  • Experimental: Arm II (deferred chemotherapy)
    Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: gemcitabine hydrochloride
    • Drug: vinblastine sulfate
    • Drug: methotrexate
    • Drug: cisplatin
    • Biological: filgrastim
Publications * Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, Agerbaek M, Dumez H, de Santis M, Théodore C, Leahy MG, Chester JD, Verbaeys A, Daugaard G, Wood L, Witjes JA, de Wit R, Geoffrois L, Sengelov L, Thalmann G, Charpentier D, Rolland F, Mignot L, Sundar S, Symonds P, Graham J, Joly F, Marreaud S, Collette L, Sylvester R; European Organisation for Research and Treatment of Cancer Genito-Urinary Cancers Group; Groupe d'Etude des Tumeurs Urogénitales; National Cancer Research Institute Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; German Association of Urologic Oncology. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):76-86. doi: 10.1016/S1470-2045(14)71160-X. Epub 2014 Dec 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 16, 2014)
285
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Israel,   Italy,   Netherlands,   Norway,   Poland,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT00028756
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE
  • 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  ICMJE
Study Chair: Cora Sternberg, Dr. San Camillo Forlanini Hospitals
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP