Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer
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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 |
- 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.
- 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 ]
| Estimated Enrollment: | 124 |
| Study Start Date: | June 2013 |
| Estimated Study Completion Date: | August 2016 |
| Estimated Primary Completion Date: | August 2015 (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:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
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:
Drug: methotrexate
Given IV
Other Names:
Drug: vinblastine
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Biological: pegfilgrastim
Given SC
Other Names:
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 |
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| United States, California | |
| USC Norris Comprehensive Cancer Center | Not yet recruiting |
| Los Angeles, California, United States, 90033 | |
| Contact: Tanya B. Dorff 323-865-0843 dorff_t@ccnt.usc.edu | |
| Principal Investigator: Tanya B. Dorff | |
| Principal Investigator: | Tanya Dorff | USC/Norris Comprehensive Cancer Center |
More Information
No publications provided
| Responsible Party: | USC/Norris Comprehensive Cancer Center |
| 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 17, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Federal Government |
Additional relevant MeSH terms:
|
Ureteral Neoplasms Urinary Bladder Neoplasms Carcinoma Carcinoma, Transitional Cell Urethral Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Urinary Bladder Diseases Urologic Diseases Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Ureteral Diseases |
Urethral Diseases Kidney Diseases Gemcitabine Cisplatin Doxorubicin Methotrexate Vinblastine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antibiotics, Antineoplastic Abortifacient Agents, Nonsteroidal Abortifacient Agents |
ClinicalTrials.gov processed this record on May 16, 2013