Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer

• Status: Not yet recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed prospectively to investigate the safety, efficacy and feasibility of cisplatin-based chemotherapy combined with tislelizumab as bladder sparing treatment for patients with muscle invasive bladder cancer (MIBC) which are eligible for cisplatin. The patients that achieved clinical remission after 4 cycles of cisplatin/gemcitabine and tislelizumab, will receive tislelizumab maintenance therapy for a year or 13 cycles. 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 investigates the efficacy of cisplatin-based chemotherapy combined with Tislelizumab to induce clinical complete remission of muscle invasive bladder cancer and the feasibility to provide bladder sparing treatment for these patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ruijin Hospital
• Treatments: Gemcitabine

Criteria

Inclusion Criteria:

• ≥ 18 and ≤75 years old on day of signing informed consent

• Signing informed consent

• Patients with histologically confirmed muscle-invasive bladder cancer (cT2-T4, N0, M0) and with strong intent to bladder sparing(Patients with mixed histology, predominantly transitional cells, could be enrolled. )

• Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 15 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.

• ECOG performance status of 0 or 1

• Adequate organ and marrow function for cisplatin treatment

• No received prior therapy with systemic chemotherapy or immunotherapy

Exclusion Criteria:

• Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• Any approved anticancer therapy within 28 days before enrollment

• Active leptomeningeal disease or uncontrolled, untreated brain metastasis

• Participants with uncontrolled hypercalcemia

• Participants with active autoimmune diseases or history of autoimmune diseases that may relapse

• History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases

• A known history of HIV infection

• Prior allogeneic stem cell transplantation or organ transplantation

• History of severe hypersensitivity reactions to other monoclonal antibodies

• History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds