Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 29
- 主要终点
- Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
研究概览
简要总结
The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC) treatments based in real world data in various European countries. The study will allow to gain insight in the true proportion of patients that fit to receive complete cisplatin-based neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients with poor prognostic factors (PS and renal function) who receive only standard treatment (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic and treatment protocol.
详细描述
There are no definitive treatment recommendations for patients diagnosed with UTUC. Radical nephroureterectomy (RNU) has been considered the gold standard treatment for UTUC. However due to the high recurrence rates reported, patients are often offered perioperative chemotherapy provided that they have a good renal function and performance status. With regard to the choice of chemotherapy treatment, there are also no clear recommendations since there are no data from randomized studies. If perioperative chemotherapy is considered in daily practice, gemcitabine/cisplatin regimen is often chosen and occasionally dd-MVAC.
The aim of this study is to explore feasibility of UTUC treatments based in real world data in various European countries. Patients who fulfil good prognostic factors (inclusion criteria for treatment randomization) will be allocated to neo-adjuvant (Arm B) or adjuvant (Arm C) chemotherapy (receiving 3 cycles of gemcitabine/cisplatin or dose dense Methotrexate, Vinblastine, Adriamycin, and Cisplatin (MVAC). Patients who don't fulfil criteria for treatment randomization will undergo Radical nephroureterectomy (RNU) only (Arm A). Patients will be followed up for 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Age > 18 years
- •Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification)
- •Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception
- •Patients without bladder cancer or with concomitant non muscle invasive bladder cancer
- •Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF <or> 55 ml/min: Electrolytes: potassium and calcium: within normal limits.
- •CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis
排除标准
- •Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
- •History of cardiovascular conditions within the past 6 months.
- •Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment.
- •Any major contraindication to a surgical procedure.
- •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- •Active infection contraindicating chemotherapy
- •Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA) <
- •Patients with past medical history of cancer can be included if diagnosed at least 4 years ago.
- •Concomitant muscle invasive bladder cancer
- •Patients who have been or still are on methotrexate treatment.
研究组 & 干预措施
Radical nephro-ureterectomy (RNU)
Patients who dont fulfil inclusion criteria for chemotherapy treatment randomization (poor renal function: Glomerular Filtration Rate (GFR) <55 ml/min or unfit for cisplatin-based chemotherapy)
干预措施: RNU (Procedure)
Gemcitabine/Cisplatin plus RNU
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery
干预措施: RNU (Procedure)
Gemcitabine/Cisplatin plus RNU
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery
干预措施: Gemcitabine/Cisplatin (Drug)
RNU plus Gemcitabine/Cisplatin
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery
干预措施: RNU (Procedure)
RNU plus Gemcitabine/Cisplatin
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery
干预措施: Gemcitabine/Cisplatin (Drug)
M-VAC protocol plus RNU
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery
干预措施: RNU (Procedure)
M-VAC protocol plus RNU
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery
干预措施: M-VAC Protocol (Drug)
RNU plus M-VAC protocol
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery
干预措施: RNU (Procedure)
RNU plus M-VAC protocol
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery
干预措施: M-VAC Protocol (Drug)
结局指标
主要结局
Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
时间窗: 6 months
Percentage of patients randomised to adjuvant or neo-adjuvant treatment
次要结局
- Disease Free Survival (DFS)(1-2 years)
- Overall Survival (OS)(1-2 years)
- Cancer-Specific Survival (CSS)(1-2 years)