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

Muscle-Invasive Bladder Carcinoma Clinical Trial

Official title:

A Prospective, Single Center Clinical Study to Examine Cisplatin-based Chemotherapy Combined With Tislelizumab as Bladder Sparing Treatment for Patients With Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04909775
• Other study ID #: RJBS-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2021
• Est. completion date: July 2023

Study information

• Verified date: May 2021
• Source: Ruijin Hospital
• Contact: Danfeng Xu
• Phone: (021)64370045
• Email: xdf12036[@]rjh.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The patients that meet the Inclusion and Exclusion Criteria will treat with 4 cycles of cisplatin-based chemotherapy combined with Tislelizumab (200mg per cycle) prior to cystectomy discussion. The patients that show clinical benefit will receive tislelizumab for bladder sparing. Forty patients will be enrolled in this trial.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle-Invasive Bladder Carcinoma
• Urinary Bladder Neoplasms

Intervention

Drug:
• Tislelizumab
200 mg per cycle, IV on day 1 of 3-week
• Cisplatin
70mg/m2 IV on Day 1 of 3-week, for 4 cycles. Dose fractionation is permissible.
• Gemcitabine
1000mg/m2, Day 1 and Day 8 of 3-week, for 4 cycles

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical complete remission rate (cCR)	The clinical complete remission rate (cCR) was defined as the proportion of patients with clinically confirmed cT0 or cTa(AJCC Cancer Staging Manual,8th ed. 2017 edition ).The cT0 or cTa was assessed by cystoscopy examination at 12 weeks after the initiation of combination therapy. Two-sided Clopper-Pearson 95% confidence intervals were constructed to evaluate the accuracy of cCR.	Up to 24 months
Secondary	Duration of cCR	Duration of cCR was defined as the delay between date of reaching cCR and tumour relapse or progression.The status of cCR was evaluated by cystoscopy examination every 3 months after the combination therapy. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.	Up to 24 months
Secondary	Bladder-intact event-free survival (BI-EFS)	Bladder-intact event-free survival (BI-EFS) was defined as the time from initiation of combination therapy to the date of occurrence of any following event : Recurrence of muscle-invasive bladder cancer based on follow-up cystoscopic evaluation; Lymph node metastases based on CT/MR/PET-CT; Distant metastases based on CT/MR/PET-CT; Bladder cancer-related death; Cystectomy due to any reason; BI-EFS will be estimated with Kaplan-Meier estimators and corresponding 95% confidence intervals.	Up to 24 months