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

Primary Purpose

Muscle-Invasive Bladder Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Cisplatin
Gemcitabine
Sponsored by
Ruijin Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscle-Invasive Bladder Carcinoma focused on measuring Bladder sparing treatment, muscle invasive bladder cancer, Tislelizumab, immunotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
May 17, 2021
Last Updated
May 30, 2021
Sponsor
Ruijin Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04909775
Brief Title
Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ruijin Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle-Invasive Bladder Carcinoma
Keywords
Bladder sparing treatment, muscle invasive bladder cancer, Tislelizumab, immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Cisplatin-based chemotherapy combined with tislelizumab
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
anti-PD-1 monoclonal antibody
Intervention Description
200 mg per cycle, IV on day 1 of 3-week
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
cis-platinum
Intervention Description
70mg/m2 IV on Day 1 of 3-week, for 4 cycles. Dose fractionation is permissible.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemcitabine Hydrochloride
Intervention Description
1000mg/m2, Day 1 and Day 8 of 3-week, for 4 cycles
Primary Outcome Measure Information:
Title
Clinical complete remission rate (cCR)
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Duration of cCR
Description
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.
Time Frame
Up to 24 months
Title
Bladder-intact event-free survival (BI-EFS)
Description
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.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Danfeng Xu
Phone
(021)64370045
Ext
666062
Email
xdf12036@rjh.com.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wenhao Lin
Phone
+8618930458051
Email
lwh970808@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danfeng Xu
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danfeng Xu
Phone
（021）64370045
Ext
666062
Email
xdf12036@rjh.com.cn
First Name & Middle Initial & Last Name & Degree
Wenhao Lin
Phone
+8618930458051
Email
lwh970808@163.com
First Name & Middle Initial & Last Name & Degree
Danfeng Xu
First Name & Middle Initial & Last Name & Degree
Lu Chen
First Name & Middle Initial & Last Name & Degree
Yi Gao
First Name & Middle Initial & Last Name & Degree
Fang Huang
First Name & Middle Initial & Last Name & Degree
Guangliang Jiang
First Name & Middle Initial & Last Name & Degree
Wenhao Lin

12. IPD Sharing Statement

Plan to Share IPD
No

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

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