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 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Last Update Posted : August 2, 2016
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| 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 |
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 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm I (immediate chemotherapy)
Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy.
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Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: gemcitabine hydrochloride Given IV
Other Names:
Drug: vinblastine sulfate Given IV
Other Names:
Drug: methotrexate Given IV
Other Names:
Drug: cisplatin Given IV
Other Names:
Biological: filgrastim Given SC
Other Names:
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Experimental: Arm II (deferred chemotherapy)
Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy.
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Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: gemcitabine hydrochloride Given IV
Other Names:
Drug: vinblastine sulfate Given IV
Other Names:
Drug: methotrexate Given IV
Other Names:
Drug: cisplatin Given IV
Other Names:
Biological: filgrastim Given SC
Other Names:
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- 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.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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
| Study Chair: | Cora Sternberg, Dr. | San Camillo Forlanini Hospitals |
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 |
| 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 |
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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 Doxorubicin Liposomal doxorubicin Methotrexate |
Vinblastine Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action 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 |