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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle-Invasive Bladder Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: Cisplatin; Drug: Gemcitabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wenhao Lin; Phone Number: +8618930458051; Email: lwh970808@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Wenhao Lin; Phone Number: +8618930458051; Email: lwh970808@163.com
      • Sub-Investigator: Wenhao Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.	Drug: Tislelizumab; 200 mg per cycle, IV on day 1 of 3-week; Other Names: anti-PD-1 monoclonal antibody; Drug: Cisplatin; 70mg/m2 IV on Day 1 of 3-week, for 4 cycles. Dose fractionation is permissible.; Other Names: cis-platinum; Drug: Gemcitabine; 1000mg/m2, Day 1 and Day 8 of 3-week, for 4 cycles; Other Names: Gemcitabine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Danfeng Xu, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 30, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 30, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; Tislelizumab; muscle invasive bladder cancer; Bladder sparing treatment
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: RJBS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No