Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: cisplatin (Drug)
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.
干预措施: gemcitabine hydrochloride (Drug)
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.
干预措施: laboratory biomarker analysis (Other)
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.
干预措施: cisplatin (Drug)
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.
干预措施: methotrexate (Drug)
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.
干预措施: vinblastine (Drug)
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.
干预措施: doxorubicin hydrochloride (Drug)
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.
干预措施: pegfilgrastim (Biological)
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.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
时间窗: Assessed up to 3 years
80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.
次要结局
- Disease-free survival(From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years)