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Withdrawn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
About this trial
This is an interventional treatment trial for Anterior Urethral Cancer
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
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
NCT ID
NCT01639521
First Posted
July 10, 2012
Last Updated
January 27, 2014
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
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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