Neoadjuvant Tislelizumab Combined With Nab-Paclitaxel Followed by Distal Ureterectomy for Ureteral Cancer: An Open-Label, Single-Center, Single-Arm, Phase II Clinical Trial (TRUCE-U01)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR)
研究概览
简要总结
This study is designed as an open-label, single-arm, single-center, phase II clinical trial, aiming to evaluate the efficacy and safety of neoadjuvant Tislelizumab combined with Nab-Paclitaxel followed by distal ureterectomy for patients with non-metastatic ureteral cancer (UTC). Patients enrolled will receive 2-3 cycles of Tislelizumab in combination with Nab-Paclitaxel every 3 weeks and then undergo distal ureterectomy (DU). The assessment of efficacy is based on the histology of specimen from DU, and treatment-related adverse events (TRAEs) will be recorded and evaluated according to CTCAE 5.0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Males or females aged no less than 18 years old;
- •Ureteral cancer indicated by ureteroscopic biopsy and imageological examination (including CT, MRI, or PET-CT), without evidences of metastasis in chest CT scan and abdominal CT scan (T1-4N0-2M0).
- •Histologically confirmed urothelial carcinoma or urothelial carcinoma as the major pathological component >50% in the specimen from ureteroscopic biopsy;
- •Suitable and planned to receive distal ureterectomy (including distal ureterectomy + partial cystectomy + ipsilateral pelvic lymph node dissection + psoas hitch procedure + ureteral reimplantation into the bladder).
- •Expected survival time of more than 12 weeks;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;
- •6.Agree to provide blood, urine, and tissue samples (for testing PD-L1 expression, tumor mutation burden, etc.); 7.The organ function levels must meet the following requirements: Hematological indicators: Absolute neutrophil count ≥1.5×10^9/L, platelet count ≥80×10^9/L, hemoglobin ≥6.0 g/dL (can be maintained through symptomatic treatment); Liver function: Total bilirubin ≤1.5 times the upper limit of normal, alanine transaminase and aspartate transaminase ≤2.5 times the upper limit of normal; Renal function: Baseline ECT renography indicates a total renal glomerular filtration rate (GFR) ≥15 ml/min, with the affected-side GFR >10 ml/min, excluding the presence of a non-functional kidney (low-level decreasing curve on dynamic renal ECT imaging) on the affected side.
- •8.Participants are willing to join the study and be able to sign and comply the protocol.
排除标准
- •Concurrent primary malignancies in other sites are excluded, except for those with a history of other malignancies that have been treated and are currently stable.
- •Confirmed bilateral upper tract urothelial carcinoma (UTUC).
- •Presence of urothelial carcinoma in the renal pelvis or bladder is excluded, except for non-muscle-invasive bladder cancer that can be completely resected via transurethral resection of bladder tumor (TURBT).
- •Received a live attenuated vaccine within 4 weeks before treatment or plan to receive during the study period;
- •Active, known or suspected history of autoimmune disease;
- •Known history of primary immunodeficiency;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- •Pregnant or breastfeeding female patients;
- •Untreated acute or chronic active Hepatitis B or Hepatitis C infection. Patients receiving antiviral therapy may be eligible if viral load is under monitored, at the discretion of the physician based on the patient's individual condition;
- •Receiving immunosuppressive medication within 4 weeks prior to starting treatment, except nasal, inhaled, topical steroids, or systemic corticosteroids at physiological doses (i.e., not exceeding 10 mg/day of prednisone or equivalent dose of other corticosteroids);
- •Known or suspected allergy to Tislelizumab or Nab-Paclitaxel;
- •Active tuberculosis;
- •Previous treatment with PD-1/PD-L1/CTLA-4 immune checkpoint inhibitors or other immunotherapies;
- •Participation in another clinical study;
- •Fertile men or women without effective contraception;
- •Uncontrolled concurrent illness, including but not limited to:
- •(1)HIV infection (HIV antibodies positive); (2)Uncontrolled severe infection; (3)Uncontrolled systemic disease (such as severe psychiatric, neurological disorders, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver, or kidney disease, uncontrolled hypertension [i.e., hypertension of CTCAE grade 2 or higher despite treatment]); (4)Active hemorrhage or newly developed thrombotic disease. (5)Renal failure with CKD grade 5 and undergoing dialysis treatment.
研究组 & 干预措施
Arm 1
Nab-Paclitaxel 125mg/m^2 IV on day 1 in combination with Tislelizumab 200mg IV on day 1 every 3 weeks for 2-3 cycles and then followed by distal ureterectomy (Distal ureterectomy + Partial cystectomy +Psoas hitch procedure + Ureteral reimplantation into the bladder + Ipsilateral pelvic lymph node dissection).
干预措施: PD-1 inhibitior (Drug)
Arm 1
Nab-Paclitaxel 125mg/m^2 IV on day 1 in combination with Tislelizumab 200mg IV on day 1 every 3 weeks for 2-3 cycles and then followed by distal ureterectomy (Distal ureterectomy + Partial cystectomy +Psoas hitch procedure + Ureteral reimplantation into the bladder + Ipsilateral pelvic lymph node dissection).
干预措施: Nab-paclitaxel (Drug)
Arm 1
Nab-Paclitaxel 125mg/m^2 IV on day 1 in combination with Tislelizumab 200mg IV on day 1 every 3 weeks for 2-3 cycles and then followed by distal ureterectomy (Distal ureterectomy + Partial cystectomy +Psoas hitch procedure + Ureteral reimplantation into the bladder + Ipsilateral pelvic lymph node dissection).
干预措施: distal ureterectomy (Procedure)
结局指标
主要结局
Pathological Complete Response (pCR)
时间窗: At the time of distal ureterectomy completed (within 14 weeks of the treatment initiated)
Defined as no residual tumor in the specimen from distal ureterectomy.
次要结局
- Treatment-related adverse events (TRAEs)(From neoadjuvant treatment initiation to 90 days after the last cycle of treatment.)
- Overall Survival (OS)(up to 5 years)
- Pathological Downstaging (pDS)(At the time of distal ureterectomy completed (within 14 weeks of the treatment initiated))
- Objective Response (OR)(After completion of neoadjuvant therapy and before distal ureterotomy.)
- Events-Free Survival (EFS)(up to 5 years)
- Recurrence-Free Survival (RFS)(up to 5 years)
- Cancer-Specific Survival (CSS)(up to 5 years)
- Nephron-Sparing Survival (NSS)(up to 5 years)