Neoadjuvant Tislelizumab + Nab-Paclitaxel Followed by Distal Ureterectomy for Ureteral Cancer

Official title

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)

Overview

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.

Interventions

• Drug PD-1 inhibitior
  Tislelizumab 200mg iv will be administered on Day 1 every 3 weeks for 2-3 cycles.
• Drug Nab-paclitaxel
  Nab-Paclitaxel 125mg/m2 IV will be administered on Day 1 every 3 weeks for 2-3 cycles
• Procedure distal ureterectomy
  Distal ureterectomy (Distal ureterectomy + Partial cystectomy +Psoas hitch procedure + Ureteral reimplantation into the bladder + Ipsilateral pelvic lymph node dissection) will be conducted after neoadjuvant treatment.

Primary outcome measures

• Pathological Complete Response (pCR) [Time frame: At the time of distal ureterectomy completed (within 14 weeks of the treatment initiated)]

Secondary outcome measures (8)

• Treatment-related adverse events (TRAEs) [Time frame: From neoadjuvant treatment initiation to 90 days after the last cycle of treatment.]
• Pathological Downstaging (pDS) [Time frame: At the time of distal ureterectomy completed (within 14 weeks of the treatment initiated)]
• Objective Response (OR) [Time frame: After completion of neoadjuvant therapy and before distal ureterotomy.]
• Events-Free Survival (EFS) [Time frame: up to 5 years]
• Overall Survival (OS) [Time frame: up to 5 years]
• Recurrence-Free Survival (RFS) [Time frame: up to 5 years]
• Cancer-Specific Survival (CSS) [Time frame: up to 5 years]
• Nephron-Sparing Survival (NSS) [Time frame: up to 5 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Hospital of Tianjin Medical University — Tianjin

Identifiers

NCT: NCT07125547 · TRUCE-U01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗