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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Arm1: Nab-Paclitaxel 125 mg/m2 IV on day 1 in combination with Tislelizumab 200mg IV on day 1 every 3 weeks for 2-3 cycles and then followed by efficacy evaluation. Patients achieved the criteria of "well response and tolerance" will undergo ureteroscopic biopsy. 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. Then, patients will receive no less than 2 cycles of maintenance therapy of Nab-Paclitaxel 125 mg/m2 IV on day 1 and Tislelizumab 200mg IV on day 1 every 3 weeks. Patients not achieved the criteria will be excluded from this study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nab-paclitaxel | Drug | 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"). |
| Measure | Description | Time Frame |
|---|---|---|
| One-year Nephron-Sparing Survival (1-year-NSS) | This is 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. Kaplan-Meier curves will be constructed to provide descriptive information on nephron-sparing survival. | up to 1 year from the initiation of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-related adverse events (TRAEs) | Treatment-related adverse events (TRAEs) ,defined as adverse events occurring from the start of treatment (C1D1) to 90 days after the completion of the last dose, including type, incidence rate, and severity grading (assessed according to the NCI-CTCAE V5.0 criteria) | From treatment initiation to 90 days after the last cycle of treatment. |
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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:
(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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hailong Hu, PhD | Contact | +86 13662096232 | Huhailong@tmu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Hailong Hu, PhD | Tianjin Medical University Second Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Hospital of Tianjin Medical University | Recruiting | Tianjin | Outside U.S. | 300211 | China |
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| ID | Term |
|---|---|
| C520255 | 130-nm albumin-bound paclitaxel |
| C000707970 | tislelizumab |
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| Tislelizumab | Drug | 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"). |
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| endoscopic intervention | Procedure | 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. |
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| Clinical Complete Response (cCR) | Defined as the achievement of a complete response (CR) based on RECIST 1.1 criteria in radiological assessment following neoadjuvant therapy, negative results on urinary cytology, absence of residual tumor in the upper urinary tract as demonstrated by ureteroscopy, and no residual tumor in the specimen from ureteroscopic biopsy. | At the time of ureteroscopic biopsy (for efficacy evaluation) completed (within 14 weeks of the treatment initiated) |
| Objective Response (OR) | Defined as the achievement of partial response (PR) or complete response (CR) based on RECIST 1.1 criteria, as assessed by imaging studies at efficacy evaluation. | After completion of the last cycle (cycle 2 or cycle 3,each cycle is 21 days) of therapy. |
| Events-Free Survival (EFS) | Defined as the time from treatment initiated to the first occurrence of delayed surgical disease progression, local tumor recurrence (including recurrence in the upper urinary tract and bladder, excluding non-muscle-invasive bladder cancer that can be resected by TURBT), distant metastasis, or death from any cause. The study will record the 1-, 2-, and 5-year EFS rates for the target population. Kaplan-Meier methods will be used to estimate the median EFS and 95% confidence interval limits, and Kaplan-Meier curves will be constructed to provide descriptive information on EFS | up to 5 years |
| Overall Survival (OS) | Defined as the time from treatment initiated to death from any cause. The study will record the 1-, 2-, and 5-year OS rates for the target population. Kaplan-Meier methods will be used to estimate the median OS and 95% confidence interval limits, and Kaplan-Meier curves will be constructed to provide descriptive information on survival. | up to 5 years |
| Recurrence-Free Survival (RFS) | Defined as the time from treatment initiated to the first occurrence of tumor recurrence (including recurrence in the upper urinary tract and bladder, excluding non-muscle-invasive bladder cancer that can be removed by TURBT). The study will record the 1-, 2-, and 5-year RFS rates for the target population. Kaplan-Meier methods will be used to estimate the median RFS and 95% confidence interval limits, and Kaplan-Meier curves will be constructed to provide descriptive information on RFS. | up to 5 years |
| Cancer-Specific Survival (CSS) | Defined as the time from enrollment to death caused by the tumor. The study will record the 1-, 2-, and 5-year CSS rates for the target population. Kaplan-Meier methods will be used to estimate the median CSS and 95% confidence interval limits, and Kaplan-Meier curves will be constructed to provide descriptive information on CSS. | up to 5 years |