A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 506
- 试验地点
- 1,733
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bevacizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine if patients with advanced transitional cell carcinoma treated with bevacizumab, gemcitabine hydrochloride (gemcitabine) and cisplatin will have increased overall survival when compared to patients treated with gemcitabine, cisplatin, and placebo.
SECONDARY OBJECTIVES:
I. To compare the progression-free survival of these two regimens in patients with advanced transitional cell carcinoma.
II. To compare the proportion of patients who experience an objective response on each regimen.
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
- Double (Participant, Investigator)
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
- •Patients must have histologically or cytologically documented metastatic or unresectable transitional cell (urothelial) carcinoma of the urinary tract (renal pelvis, ureter, bladder, prostate, or urethra), with metastatic or locally advanced disease (T4b, N2, N3, or M1); patients must not be candidates for potentially curative surgery or radiotherapy
- •For patients that have had surgical resection prior to study enrollment, residual or unresected disease (measurable and/or unmeasurable) must be evident on post-surgical scans
- •Prior treatment for transitional cell carcinoma (TCC)
- •Patients may not have received combination systemic chemotherapy for metastatic disease
- •For the purposes of this study, radiosensitizing single agent chemotherapy is not considered prior systemic therapy
- •Prior neoadjuvant or adjuvant systemic chemotherapy is permissible provided the interval from end of therapy to diagnosis of metastatic disease is at least 1 year
- •>= 4 weeks since any prior radiation (including palliative) or major surgery and fully recovered
- •>= 7 days since any minor surgery such as port placement
- •>= 4 weeks since any intravesical therapy
- •No prior treatment with bevacizumab or other angiogenesis inhibitors
- •No known history of brain metastases; brain imaging (magnetic resonance imaging [MRI]/computed tomography [CT]) is not required
- •No current congestive heart failure; New York Heart Association (NYHA) class II, III or IV
- •Patients with history of hypertension must be well controlled (< 150/90) on a regimen of anti-hypertensive therapy
- •Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range international normalized ratio (INR) (usually between 2 and 3) or be on a stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible
- •No significant history of bleeding events or gastrointestinal (GI) perforation
- •Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible
- •Patients with a history of GI perforation within 12 months of registration are not eligible
- •Patients with a history of peritoneal carcinomatosis are not eligible
- •No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible
- •Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study
- •No serious or non-healing wound, ulcer, or bone fracture
- •No sensory or motor peripheral neuropathy >= grade 2
- •Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
- •Patients that are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to registration
- •For women of child-bearing potential with an elevated beta-HCG that is believed to be related to cancer and not pregnancy, a negative trans-vaginal ultrasound and gynecological examination are required
- •Women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (or Karnofsky performance status [KPS] >= 80)
- •Absolute neutrophil count (ANC) >= 1,500/uL
- •Platelet count >= 100,000/uL
- •Calculated or measured creatinine clearance >= 50 mL/minute
- •Bilirubin =< 1.25 times upper limits of normal; for patients with Gilbert's disease, =< 2.5 x upper limit of normal (ULN) is allowed
- •Aspartate aminotransferase (AST) =< 2.0 x upper limits of normal
- •Urine protein to creatinine ratio < 1.0 or urine protein =< 1+ or 24-hour urine protein =< 1 gram
排除标准
- 未提供
研究组 & 干预措施
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine Hydrochloride (Drug)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Bevacizumab (Biological)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Gemcitabine Hydrochloride (Drug)
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Placebo Administration (Other)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days 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
Overall Survival (OS)
时间窗: From date of randomization to date of death due to any cause, assessed up to 7 years
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.The stratified log-rank statistic will be the primary analysis to compare the two treatment arms on OS with the stratification factors: presence of visceral metastases (no, yes) and prior chemotherapy (no, yes). In addition, the proportional hazards model will be used to assess the importance of the treatment arm adjusting on patient characteristics, stratification variables and other important covariates in predicting OS.
次要结局
- Progression-free Survival (PFS)(From the date of randomization to date of progression or death due to any cause, whichever occurs first, assessed up to 7 years)
- Objective Response(Up to 7 years)
- Number of Patients Experiencing Grade 3+ Toxicity(Up to 7 years)