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

Primary Purpose

Anterior Urethral Cancer, Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, Posterior Urethral Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cisplatin
gemcitabine hydrochloride
methotrexate
vinblastine
doxorubicin hydrochloride
pegfilgrastim
laboratory biomarker analysis
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anterior Urethral Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Arm A (gemcitabine hydrochloride, cisplatin)

    Arm B (MVAC)

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
    80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.

    Secondary Outcome Measures

    Disease-free survival

    Full Information

    First Posted
    July 10, 2012
    Last Updated
    January 27, 2014
    Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01639521
    Brief Title
    Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer
    Official Title
    Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funding
    Study Start Date
    May 2013 (undefined)
    Primary Completion Date
    May 2013 (Actual)
    Study Completion Date
    May 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Southern California
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A (gemcitabine hydrochloride, cisplatin)
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Arm B (MVAC)
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    cisplatin
    Other Intervention Name(s)
    CACP, CDDP, CPDD, DDP
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    gemcitabine hydrochloride
    Other Intervention Name(s)
    dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    methotrexate
    Other Intervention Name(s)
    amethopterin, Folex, methylaminopterin, Mexate, MTX
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    vinblastine
    Other Intervention Name(s)
    Velban, Velsar, VLB
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    doxorubicin hydrochloride
    Other Intervention Name(s)
    ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
    Intervention Description
    Given IV
    Intervention Type
    Biological
    Intervention Name(s)
    pegfilgrastim
    Other Intervention Name(s)
    Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF
    Intervention Description
    Given SC
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    Correlative studies
    Primary Outcome Measure Information:
    Title
    Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
    Description
    80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.
    Time Frame
    Assessed up to 3 years
    Secondary Outcome Measure Information:
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Tanya Dorff
    Organizational Affiliation
    University of Southern California
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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