Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
Upper tract urothelial cancer (UTUC) is cancer in the lining of the kidney or ureter (the tube that drains the kidney). This type of cancer is rare and as a result, there are only a few studies that have looked at it.
Standard of care for UTUC would be surgery followed by chemotherapy (adjuvant chemotherapy). However, we know from studies that have looked at cancer of the lining of the bladder, which is a similar cancer in many ways, that treating people with chemotherapy before surgery (neoadjuvant chemotherapy) can lead to longer survival compared to the standard of care. There are no studies to show this in UTUC. Neoadjuvant chemotherapy is thought to help improve survival by treating any cancer that may have spread from the original tumour but that is not visible yet on scans. This study would be the first clinical trial in Canada to evaluate the use of chemotherapy before surgery in this disease setting.
Since UTUC is rare, the purpose of this study is to determine if it is possible to enrol enough patients to a trial looking at the use of chemotherapy before surgery.
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
- •Newly diagnosed radiographically visible (CT or MRI) cT1-4 N0 M0 with positive selective urinary cytology, positive bladder urinary cytology, or endoscopic biopsy for high grade urothelial cell carcinoma
- •Age ≥18 years of age
- •Eastern Cooperative Oncology Group (ECOG) score 0-1
- •Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per participating site attending urologic oncologist
- •Medically appropriate candidate for cisplatin-based chemotherapy as per participating site attending medical oncologist
- •Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST < 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 60 mL/min
- •Patients who are randomized to the adjuvant chemotherapy will be reassessed for suitability to receive adjuvant chemotherapy after definitive surgery (nephroureterectomy or ureterectomy) based on the following criteria:
- •pT2-4 N0-3 M0 or pT any N1-3 M0 with predominant urothelial component
- •ECOG score 0-2
- •Medically appropriate candidate for platin-based chemotherapy as per participating site attending medical oncologist
- •Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST < 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 30 mL/min
排除标准
- •Metastatic disease
- •Radiographically visible nodal disease
- •Concurrent muscle-invasive bladder cancer (non-muscle invasive bladder cancer is acceptable)
- •Solitary kidney
- •Other cancer diagnosis or systemic chemotherapy use within 2 years of study enrollment (prior bladder cancer and intravesical therapy allowed)
- •Concomitant diseases that are a formal exclusion to cisplatin chemotherapy (deafness, ≥ grade II neuropathy, serious active infection)
- •Concomitant use of any other investigational drugs
- •Pregnancy or breast feeding (you must remain on contraception, not father a child or donate sperm while receiving gemcitabine/cisplatin and for 6 months following the last dose)
研究组 & 干预措施
Adjuvant Chemotherapy Arm (Standard of Care)
Patients will undergo surgical intervention (nephroureterectomy or ureterectomy) followed by adjuvant chemotherapy.
Patients with a GFR greater or equal to 60 mL/min will receive Gemcitabine/Cisplatin while those with a GFR greater or equal to 30 mL/min but less than 60 mL/min will receive Gemcitabine/Carboplatin.
Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles.
Gemcitabine/Carboplatin will be administered on a 3-week cycle for up to 4 cycles.
干预措施: Gemcitabine (Drug)
Neoadjuvant Chemotherapy Arm
Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles. This will be followed by surgical intervention (nephroureterectomy or ureterectomy).
干预措施: Gemcitabine (Drug)
Neoadjuvant Chemotherapy Arm
Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles. This will be followed by surgical intervention (nephroureterectomy or ureterectomy).
干预措施: Cisplatin (Drug)
Adjuvant Chemotherapy Arm (Standard of Care)
Patients will undergo surgical intervention (nephroureterectomy or ureterectomy) followed by adjuvant chemotherapy.
Patients with a GFR greater or equal to 60 mL/min will receive Gemcitabine/Cisplatin while those with a GFR greater or equal to 30 mL/min but less than 60 mL/min will receive Gemcitabine/Carboplatin.
Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles.
Gemcitabine/Carboplatin will be administered on a 3-week cycle for up to 4 cycles.
干预措施: Cisplatin (Drug)
Adjuvant Chemotherapy Arm (Standard of Care)
Patients will undergo surgical intervention (nephroureterectomy or ureterectomy) followed by adjuvant chemotherapy.
Patients with a GFR greater or equal to 60 mL/min will receive Gemcitabine/Cisplatin while those with a GFR greater or equal to 30 mL/min but less than 60 mL/min will receive Gemcitabine/Carboplatin.
Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles.
Gemcitabine/Carboplatin will be administered on a 3-week cycle for up to 4 cycles.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: 36 months
DFS is defined as the time from randomization to development of intravesical recurrence, contralateral upper tract recurrence or distant metastasis
Rate of complete pathologic response
时间窗: 36 months
Complete pathologic response is defined as pT0 N0
Feasibility of enrolling cT1-4N0 M0 UTUC patients in a randomized trial of neoadjuvant chemotherapy versus standard of care by assessing pilot trial recruitment rates
时间窗: 24 months
次要结局
- Number of patients randomized per site per month(24 months)
- Site-specific enrolment rate(24 months)
- Number of patients approached per site per month(24 months)