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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This study has been withdrawn prior to enrollment.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)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01639521
First received: July 10, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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
Endpoint Classification: Safety Study
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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]

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:

PRIMARY OBJECTIVES

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.

SECONDARY OBJECTIVES

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01639521

Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Tanya Dorff University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01639521     History of Changes
Other Study ID Numbers: 4B-10-5, NCI-2012-00961
Study First Received: July 10, 2012
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urethral Neoplasms
Urinary Bladder Neoplasms
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Ureteral Diseases
Urethral Diseases
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Cisplatin
Doxorubicin
Gemcitabine
Liposomal doxorubicin
Methotrexate
Vinblastine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents

ClinicalTrials.gov processed this record on November 20, 2014