Nephron-sparing Treatment of Tislelizumab + Nab-Paclitaxel for Renal Pelvic Cancer

Official title

Nephron-sparing Treatment Combining Tislelizumab and Nab-Paclitaxel for Renal Pelvic Cancer: An Open-Label, Single-Center, Single-Arm, Phase II Clinical Trial (TRUCE-U03)

Overview

This study is designed as an open-label, single-arm, single-center, phase II clinical trial, aiming to evaluate the efficacy of nephron-sparing treatment combining Tislelizumab and Nab-Paclitaxel for HER-2 expressing renal pelvic cancer (RPC) . Patients enrolled will receive 2-3 cycles of Tislelizumab in combination with Nab-Paclitaxel every 3 weeks and then undergo evaluation. Patients who achieve all of the following criteria of "well response and tolerance" will receive further maintenance treatment: (1)The patient achieves a complete response (CR) or partial response (PR) according to the RECIST 1.1 criteria, indicating that the tumor is well-controlled. (2) If the patient has residual lesions, it should be confirmed by the clinical physician that these lesions can be eliminated through laser ablation via ureteroscopy. (3)The patient has not experienced any treatment-related adverse events (TRAEs) that warrant discontinuation of therapy during systemic treatment. (4)The patient is willing to undergo further maintenance therapy. If the patient meets all the criteria above, ureteroscopic biopsy should be performed. If residual lesions are detected under the ureteroscope, endoscopic intervention (e.g., laser ablation, cryoablation) should be carried out simultaneously to eliminate these residual lesions. Patients who meet the above criteria will proceed with no less than 2 cycles of maintenance systemic therapy (Tislelizumab + Nab-Paclitaxel). Patients who do not meet the criteria will be excluded from the study and are recommended to undergo salvage radical nephroureterectomy (RNU) as soon as possible. One-year Nephron-Sparing Survival (1 year-NSS): Defined as the absence of surgical indications for nephrectomy due to progression or recurrence of upper urinary tract urothelial carcinoma, distant metastasis caused by the primary upper urinary tract tumor, or death from any cause within 1 year from the initiation of treatment. Treatment-related adverse events (TRAEs) will be recorded and evaluated according to CTCAE 5.0.

Interventions

• Drug Nab-paclitaxel
  Nab-Paclitaxel 125 mg/m2 IV will be administered on Day 1 every 3 weeks for 2-3 cycles before evaluation, then on Day 1 every 3 weeks for maintenance therapy after evaluation (only for patients who achieved the criteria of "well response and tolerance").
• Drug Tislelizumab
  Tislelizumab 200mg iv will be administered on Day 1 every 3 weeks for 2-3 cycles before evaluation, then on Day 1 every 3 weeks for 3-6 cycles as maintenance therapy after evaluation (only for patients achieved the criteria of "well response and tolerance").
• Procedure endoscopic intervention
  Patients who achieved the criteria of "well response and tolerance", but with residual lesions will receive endoscopic intervention (e.g., laser ablation, cryoablation) via ureteroscopy.

Primary outcome measures

• One-year Nephron-Sparing Survival (1-year-NSS) [Time frame: up to 1 year from the initiation of treatment.]

Secondary outcome measures (7)

• Treatment-related adverse events (TRAEs) [Time frame: From treatment initiation to 90 days after the last cycle of treatment.]
• Clinical Complete Response (cCR) [Time frame: At the time of ureteroscopic biopsy (for efficacy evaluation) completed (within 14 weeks of the treatment initiated)]
• Objective Response (OR) [Time frame: After completion of the last cycle (cycle 2 or cycle 3，each cycle is 21 days） of therapy.]
• 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]

Eligibility criteria

Inclusion criteria

• Males or females aged no less than 18 years old;
• Suitable and planned to undergo laser ablation of renal pelvic tumors via ureteroscopy;
• The tumor is located in the renal pelvis, diagnosed as upper tract urothelial carcinoma based on ureteroscopic biopsy, urinary cytology, or imaging examinations (CT, MRI, or PET-CT), without lymph node metastasis or distant metastasis, with a clinical stage of T1-2N0M0. Additionally, requiring maximum tumor diameter is less than 3 cm.
• Expected survival time of more than 12 weeks;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;
• Agree to provide blood, urine, and tissue samples (for testing PD-L1 expression, HER-2, tumor mutation burden, etc.);
• 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.

• 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 ureter 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: NCT07233252 · TRUCE-U03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗