A Prospective Phase III Randomized Clinical Trial Comparing the Effectiveness of Immediate Postoperative Intravesical Instillation With Either Gemcitabine Hydrochloride or Epirubicin Hydrochloride in Patients With Urinary Bladder Cancer (Gemcitabine Epirubicin Normal SAline)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Bladder cancer recurrence
研究概览
简要总结
The natural history of non-muscle-invasive bladder cancer is characterised by recurrence and progression. We compare the effectiveness of gemcitabine hydrochloride and epirubicin hydrochloride, in combination with continuous saline irrigation, as an immediate single intravesical instillation in the potential reduction of the disease recurrence as well as progression.
详细描述
Bladder cancer (BLCa) is the seventh most commonly diagnosed cancer in the male population worldwide, while it drops to tenth when both genders are considered. At diagnosis about 75% of the patients suffer from non-muscle-invasive BLCa. The natural history of this disease is characterised by recurrence and progression. In order to reduce the possibilities for recurrence, and therefore progression, an immediate single intravesical instillation (ISIVI) of a chemotherapeutic agent has been shown to act by destroying circulating tumour cells after transurethral resection of urinary bladder tumors (TURB), and by an ablative effect on residual tumour cells at the resection site and on small overlooked tumours. Several agents, among them gemcitabine and epirubicin, have been used for the ISIVI so far. Moreover, four large meta-analyses comprising 1,476 to 3,103 patients have consistently shown that after TURB, ISIVI significantly reduces the recurrence rate compared to TURB alone. Furthermore, two meta-analyses suggest efficacy of continuous saline irrigation (CSI) in the prevention of early recurrences. The prevention of tumour cell implantation should be initiated within the first few hours after TURB. After that, tumour cells are firmly implanted and are covered by the extracellular matrix. In all ISIVI studies, the instillation was administered within 24 hours. Until today, no randomised comparisons of individual drugs, combined or not with CSI, have been conducted.
After the initial TURB, the patients will be treated with CSI for 24 hours. Then, they will be randomised, either to gemcitabine or epirubicin, and within 6 hours after the TURB they will receive an ISIVI with gemcitabine or epirubicin, as follows:
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GROUP A: Gemcitabine hydrochloride 2gr in 100ml 0.9% NaCl for 45-60 minutes
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GROUP B: Epirubicin hydrochloride 50mg in 50ml 0.9% NaCl for 45-60 minutes
During the ISIVI the CSI will be stopped.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary urinary bladder tumor
- •Secondary urinary bladder tumor (recurrence)
- •Bipolar or monopolar resection
- •Creat <2.2mg/dl
- •35% <Hct <52%
- •White bloode cells count WBC ≥3000 / μL
- •75000 <PLT <500000 / μL
- •Urine culture: negative / sterile
- •Alkaline phosphatase, total bilirubin, SGOT, SGPT: values as high as 2 times above the upper normal limit
- •Good clinical condition (according to Eastern Cooperative Oncology Group PS ≤ 1)
- •CT Urography without findings suggesting an upper urinary tract tumor in the last 3 months before the transurethral resection of the bladder tumor
排除标准
- •More than 2 low grade / high differentiation (low grade / LG) histologically confirmed bladder tumors in the last 18 months before the transurethral resection of the bladder tumor
- •High grade / low differentiation (HG) histologically confirmed bladder tumor in the last 9 months before the transurethral resection of the bladder tumor
- •Those who undergo a transurethral resection of a bladder tumor according to the Guidelines of the European Association of Urology for non-muscle-invasive bladder cancer: incomplete resection of tumor, absence of muscle fibers in the sample with the exception of: Ta / LG-G1, primary Cis and finally, pT1 tumors
- •Intravesical instillation of chemotherapeutic agent or BCG in the last 6 months before the transurethral resection of the bladder tumor
- •History of non-urothelial bladder cancer
- •Stage of disease pT2 (muscle-invasive bladder cancer)
- •Presence of a tumor in the urethra
- •Upper urinary tract malignancy (present or anamnestically)
- •History of pelvic radiotherapy
- •Histrory of another malignancy in the last 5 years before the transurethral resection of the bladder tumor
研究组 & 干预措施
Gemcitabine
Bladder cancer patients, who are treated with a transurethral resection of a bladder tumor, receive postoperatively, within 6 hours after the resection, an immediate single intravesical instillation with gemcitabine hydrochloride 2gr in 100ml of saline for 45-60 minutes and continuous saline irrigation for 24 hours
干预措施: Gemcitabine Hydrochloride combined with continuous saline irrigation (Drug)
Epirubicin
Bladder cancer patients, who are treated with a transurethral resection of a bladder tumor, receive postoperatively, within 6 hours after the resection, an immediate single intravesical instillation with epirubicine hydrochloride 50mg in 50ml of saline for 45-60 minutes and continuous saline irrigation for 24 hours
干预措施: Epirubicin Hydrochloride combined with continuous saline irrigation (Drug)
结局指标
主要结局
Bladder cancer recurrence
时间窗: At 12 months after the transurethral resection of a bladder tumor
Histologically proven bladder cancer recurrence
Bladder cancer progression
时间窗: At 12 months after the transurethral resection of a bladder tumor
Histologically proven bladder cancer progression
次要结局
- Bladder cancer recurrence(At 24 months after the transurethral resection of a bladder tumor)
- Bladder cancer progression(At 24 months after the transurethral resection of a bladder tumor)
研究者
Vasileios Tzortzis
Professor of Urology
University of Thessaly