This study is designed prospectively to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC). Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071). This trial focuses on the efficacy of Tislelizumab in combination with cisplatin-based chemotherapy to induce pathological down-staging of locally advanced UTUC in neoadjuvant setting.
Neoadjuvant therapy of cisplatin-based chemotherapy has been proved to improve prognosis of muscle invasive UTUC patients in several studies. This study is designed to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before radical nephroureterectomy and lymphadenectomy. Drug: Tislelizumab 200 mg per cycle, IV on day 14 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy Other Names: • anti-PD-1 monoclonal antibody Drug: Cisplatin 70mg/m2 IV on day 2of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy. Dose fractionation is permissible. Drug: Gemcitabine 1000mg/m2 IV on day 1 and Day 8 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy
Shanghai Renji Hospital
Shanghai, Shanghai Municipality, China
Pathological complete response rate
the absence of visible lesion of carcinoma (ypT0/Tis) and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen
Time frame: 30 days after surgery
Pathologic response rate
The rate of patients that reach pathological downstaging at the time of nephroureterectomy.
Time frame: 30 days after surgery
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