Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer
Keywords
Abstract
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.
Dates
| Last Verified: | 12/31/2013 |
| First Submitted: | 07/09/2012 |
| Estimated Enrollment Submitted: | 07/10/2012 |
| First Posted: | 07/11/2012 |
| Last Update Submitted: | 01/26/2014 |
| Last Update Posted: | 01/28/2014 |
| Actual Study Start Date: | 04/30/2013 |
| Estimated Primary Completion Date: | 04/30/2013 |
| Estimated Study Completion Date: | 04/30/2013 |
Condition or disease
Intervention/treatment
Drug: cisplatin
Drug: Arm A (gemcitabine hydrochloride, cisplatin)
Drug: Arm B (MVAC)
Drug: Arm B (MVAC)
Drug: Arm B (MVAC)
Biological: Arm B (MVAC)
Other: laboratory biomarker analysis
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| 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: Arm A (gemcitabine hydrochloride, cisplatin) Given IV |
| 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: Arm B (MVAC) Given IV |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| 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 |
Outcome
Primary Outcome Measures
1. Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0 [Assessed up to 3 years]
Secondary Outcome Measures
1. Disease-free survival [From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years]
