NCT05445648

Comprehensive Bladder Preservation Therapy on Patients With Muscle Invasive Bladder Cancer

Immune Checkpoint Inhibitor in Addition to Transurethral Resection of Bladder Cancer (TUBRT) and Radiation Therapy in Patients With cT2-4aN0M0 Bladder Cancer: a Mono-centre Clinical Study

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Nowadays, Immune Checkpoint Inhibitor (ICI) has become one of the new drugs for the treatment of advanced uroepithelial carcinoma. The Food and Drug Administration (FDA) approved ICI for bladder cancer (BC) patients who cannot tolerate cisplatin chemotherapy and whose tumors express programmed cell death protein ligand-1 (PD-L1). However, the efficacy of ICI in bladder preservation therapy for muscular invasive bladder cancer (MIBC) is unknown. With the progressive clinical confirmation of the efficacy of immunotherapy, ICI has moved from second-line to first-line treatment in the indication of advanced unresectable BC. It even has been used in the neoadjuvant and postoperative adjuvant therapy for MIBC and non-muscle invasive bladder cancer (NMIBC) where Bacillus Calmette-Guérin (BCG) therapy has failed. Available studies have shown that neoadjuvant immunotherapy can achieve a pathological complete response (pCR) of 31%-42% for MIBC, regardless of using a single drug or combination, which is higher than that of neoadjuvant chemotherapy, and the incidence of side effects associated with neoadjuvant immunotherapy is lower than that of neoadjuvant chemotherapy, providing an effective treatment option for cisplatin-intolerant patients. Studies have shown that radiotherapy leads to immunogenic cell death, which results in the release and presentation of tumor antigens and directs the recruitment and activation of T cells. It also induces increased expression of PD-L1 in tumor cells, which in turn improves the efficacy of immunotherapy. Thus ICI combined with radiotherapy has a synergistic antitumor effect and does not produce serious toxic side effects similar to those associated with chemotherapeutic agents. This study proposes a novel neoadjuvant immunotherapy-based integrated bladder preservation therapy (neoadjuvant immunotherapy + TURBT + postoperative adjuvant radiotherapy combined with immunotherapy) and investigates the effectiveness and safety of this strategy in bladder preservation treatment strategy.

Detailed description

This study aims to investigate the efficacy and safety of a comprehensive immunotherapy-based bladder preservation treatment strategy (neoadjuvant immunotherapy + TURBT + adjuvant radiation therapy (RT) combined with immunotherapy) by implementing a prospective, single-arm, single-center, open clinical trial. It aims to: 1) assess pCR (pathological complete remission rate) and pathological stage reduction rate of patients with MIBC after neoadjuvant immunotherapy. 2) assess relative risk factors that have an impact on pathological stage reduction rate and pCR. 3) assess bladder preservation rate of MIBC patients after the immunotherapy-based integrated bladder preservation therapy. 4) assess tumor recurrence-free survival, progression-free survival, and tumor-specific and overall survival rates after treatment. 5) To assess the safety of this treatment. 6) To collect tumor tissues from TURBT and study genetic variations as well as the expression of relevant biomarkers.

Conditions

• Urinary Bladder Neoplasms

Interventions

Type	Name	Description
DRUG	Tislelizumab Injection	After patient recruitment, every patient first receives a regimen of tislelizumab injection 200 mg every time , q3w, 4 times in total. Then all patients, if operable, undergo TURBT. The first day after TURBT, patients again start to receives a regimen of tislelizumab Injection 200 mg every time , q3w, 4 times in total. Meanwhile, on the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.
PROCEDURE	Transurethral resection of bladder tumor	After the initial tislelizumab injection regimen, patients undergo clinical assessment and receive transurethral resection of bladder tumor if operable.
RADIATION	Adjuvant radiotherapy	On the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.

Timeline

• Start date: 2023-02-01
• Primary completion: 2024-02-01
• Completion: 2026-02-01
• First posted: 2022-07-06
• Last updated: 2022-12-28

Locations

1 site across 1 country: China