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

NCT ID: NCT01639521

Last Updated: 2014-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2013-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

cisplatin

Intervention Type DRUG

Given IV

gemcitabine hydrochloride

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

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.

Group Type EXPERIMENTAL

cisplatin

Intervention Type DRUG

Given IV

methotrexate

Intervention Type DRUG

Given IV

vinblastine

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

pegfilgrastim

Intervention Type BIOLOGICAL

Given SC

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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cisplatin

Given IV

Intervention Type DRUG

gemcitabine hydrochloride

Given IV

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

vinblastine

Given IV

Intervention Type DRUG

doxorubicin hydrochloride

Given IV

Intervention Type DRUG

pegfilgrastim

Given SC

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CACP CDDP CPDD DDP dFdC difluorodeoxycytidine hydrochloride gemcitabine Gemzar amethopterin Folex methylaminopterin Mexate MTX Velban Velsar VLB ADM ADR Adria Adriamycin PFS Adriamycin RDF Filgrastim SD-01 GCSF-SD01 Neulasta SD-01 sustained duration G-CSF

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tanya Dorff

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Other Identifiers

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NCI-2012-00961

Identifier Type: REGISTRY

Identifier Source: secondary_id

4B-10-5

Identifier Type: -

Identifier Source: org_study_id

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