A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 261
- 试验地点
- 61
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
POUT is a multi-centred randomised controlled phase III trial. 345 patients who have undergone nephro-ureterectomy, are surgically staged pT2-pT4, N0-3 or are pT1 and node positive, and who are fit for adjuvant chemotherapy, will be randomised to four cycles of adjuvant platinum based chemotherapy (experimental group) or surveillance (control group). Participants will be followed up according to routine practice.
Primary endpoint: Disease-free survival (DFS)
Secondary endpoints:
- Overall Survival
- Metastasis free survival
- Incidence of bladder second primary tumours
- Incidence of contralateral primary tumours
- Acute and late toxicity
- Treatment compliance
- Quality of life
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
- •Written informed consent
- •≥18 years of age
- •Post radical nephro-ureterectomy for upper tract tumour with predominant TCC component - squamoid differentiation or mixed TCC/SCC is permitted.
- •Histologically confirmed TCC staged pT2-pT4 pN0-3 M0 or pTany N1-3 M0 (providing all grossly abnormal nodes are resected). Patients with microscopically positive margins on pathology may be entered (providing all grossly abnormal disease was resected).
- •Satisfactory haematological profile (ANC> 1.5 x 109/L, platelet count ≥ 100 x 109/L) and liver function tests (bilirubin < 1.5 x ULN, AST and Alkaline phosphatase < 2.5 x ULN), Glomerular filtration rate ≥30 mls/min.
- •Fit and willing to receive adjuvant chemotherapy with first cycle to be commenced within 90 days of radical nephro-ureterectomy if allocated
- •WHO performance status 0-
- •Available for long-term follow-up
排除标准
- •Evidence of distant metastases
- •Pure adenocarcinoma, squamous cell carcinoma or small cell or other variant histology
- •Un-resected macroscopic nodal disease
- •Concurrent muscle invasive bladder cancer (patients with concurrent Non-muscle invasive bladder cancer (NMIBC) will be eligible)
- •GFR <30 ml/minute. NB Gemcitabine-carboplatin can only be given for patients with suboptimal renal function for cisplatin i.e. for GFR 30-49ml/min. Patients with poor performance status or co-morbidities that would make them unfit for chemotherapy are ineligible for the trial
- •Significant co-morbid conditions that would interfere with administration of protocol treatment
- •Pregnancy; lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception (male patients should also use contraception if sexually active);
- •Previous malignancy in the last 5 years except for previous NMIBC, adequately controlled non melanoma skin tumours, CIS of cervix or LCIS of breast or localised prostate cancer in patients who have a life expectancy of over 5 years upon trial entry.
研究组 & 干预措施
Surveillance
Patients allocated to surveillance will be seen at 4, 7, 10 and 13 weeks post randomisation - equivalent to the end of cycle in patients receiving chemotherapy - in order to collect details of early treatment failure in this group and comparative data relating to toxicity and quality of life. Patients on surveillance will then be followed up for signs of recurrence at the same intervals as those who received chemotherapy
干预措施: Surveillance (Other)
Chemotherapy
Patients allocated adjuvant chemotherapy will receive 4 x 21 day cycles of gemcitabine-cisplatin. Patients who have a sub-optimal renal function (GFR 30-49ml/min) will receive carboplatin instead of cisplatin.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: 3 years
To determine whether adjuvant combination chemotherapy improves the disease-free survival for patients with resected histologically confirmed muscle invasive (pT2-T4, N0-3) or node positive upper tract TCC.
次要结局
- Quality of life (QoL)(Patients' QoL will be assessed over 2 years)
- Overall survival(Patients followed-up for 5 years)
- Metastasis free survival(Patients are followed up for 5 years)
- Acute and late toxicity(Patients are followed up for 5 years)
- Incidence of bladder second primary tumours(Patients are followed up for 5 years)
- Incidence of contralateral primary tumours(Patients are followed up for 5 years)