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Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

This study has been withdrawn prior to enrollment.
(Lack of funding)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Southern California Identifier:
First received: July 10, 2012
Last updated: January 27, 2014
Last verified: January 2014
This study is about two chemotherapy study drug combinations (regimens) that are used for urothelial (bladder or upper urinary tract) cancer. Both study drug regimens, gemcitabine (gemcitabine hydrochloride) plus cisplatin, and high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin plus cisplatin), are standard chemotherapy regimens. Both regimens are used to treat people with urothelial cancer that has spread to other organs. Both study drug regimens have been proven to be effective in lowering the risk of the cancer coming back, but it is not known which regimen is the best. This study hopes to learn whether there is a difference in the effectiveness and side effects of these two study drug regimens when they are given to people who have had their urothelial cancer completely removed.

Condition Intervention Phase
Anterior Urethral Cancer
Localized Transitional Cell Cancer of the Renal Pelvis and Ureter
Posterior Urethral Cancer
Recurrent Bladder Cancer
Recurrent Urethral Cancer
Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Stage III Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Ureter Cancer
Urethral Cancer Associated With Invasive Bladder Cancer
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: methotrexate
Drug: vinblastine
Drug: doxorubicin hydrochloride
Biological: pegfilgrastim
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC

Resource links provided by NLM:

Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0 [ Time Frame: Assessed up to 3 years ]
    80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.

Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years ]

Enrollment: 0
Study Start Date: May 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (gemcitabine hydrochloride, cisplatin)
Patients receive cisplatin IV on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (MVAC)
Patients receive methotrexate IV on day 1 and vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV on day 2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: vinblastine
Given IV
Other Names:
  • Velban
  • Velsar
  • VLB
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


To estimate the difference in the rate of unacceptable toxicity for dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin (GC) in the adjuvant treatment of urothelial cancer.


To compare rates of disease recurrence at 3 years between dose-dense MVAC and GC.

To determine whether molecular markers excision repair cross-complementing-1 (ERCC-1) ribonucleoside-diphosphate reductase M-1 (RRM-1), breast cancer 1 (BRCA1) topoisomerase 2-alpha (Top2A) and protein 53 (p53) can predict those patients more likely to benefit from chemotherapy.

To investigate the potential utility of cytidine deaminase (CDA), ERCC-1, xeroderma pigmentosum group D (XPD), glutathione S-transferase P-1 (GSTP-1) and glutathione S-transferase M-1 (GSTM-1) as molecular markers which predict occurrence of significant toxicity during adjuvant chemotherapy for urothelial cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cisplatin intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive methotrexate IV on day 1, vinblastine IV, doxorubicin hydrochloride IV, cisplatin IV on day 2 and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed high-grade urothelial carcinoma, stage T3bN0, T4N0 or any T stage with lymph node involvement, completely resected; including upper tract urothelial carcinoma
  • The dominant histology must be transitional cell or urothelial but foci of other histologies less than 20 percent of the total tumor volume are permitted
  • Absence of metastatic disease on radiographic imaging
  • Patients must be enrolled and able to start treatment within 90 days of radical cystectomy or radical nephrectomy
  • Creatinine less than institutional upper limit of normal (ULN) or clearance greater or equal to 50 mL/min (may be calculated by Cockcroft-Gault formula or measured from 24-hour urine collection)
  • Serum total bilirubin less or equal to 1.5 x ULN (except for patients with Gilbert's)
  • Alkaline phosphatase less or equal to 2.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) less or equal to 2.5 x ULN
  • White blood cells (WBC) greater or equal to 3000
  • Absolute neutrophil count (ANC) greater or equal to 1500
  • Hemoglobin (Hb) greater or equal to 9
  • Platelets greater or equal to 100,000
  • Normal left ventricular ejection fraction, by echocardiogram or multi gated acquisition scan (MUGA)
  • Patients must be recovered from surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Willing and able to provide informed consent
  • Willingness to use barrier contraception during study period

Exclusion Criteria:

  • The presence of significant pleural effusion or ascites
  • Prior systemic chemotherapy for urothelial carcinoma including neoadjuvant chemotherapy (prior intravesical therapy is permitted)
  • History of malignancy within preceding 5 years, aside from non-melanoma skin cancer or previously treated or incidentally detected prostate cancer with undetectable PSA (after radical cystectomy or prostate cancer therapy)
  • Peripheral neuropathy greater than grade 1
  • The presence of active heart disease such as congestive heart failure or unstable angina
  Contacts and Locations
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Please refer to this study by its identifier: NCT01639521

Sponsors and Collaborators
University of Southern California
National Cancer Institute (NCI)
Principal Investigator: Tanya Dorff University of Southern California
  More Information

Responsible Party: University of Southern California Identifier: NCT01639521     History of Changes
Other Study ID Numbers: 4B-10-5
NCI-2012-00961 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Study First Received: July 10, 2012
Last Updated: January 27, 2014

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Kidney Diseases
Ureteral Diseases
Liposomal doxorubicin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors processed this record on May 22, 2017