Evaluation of PD-L1 Expression and Immune Infiltration in High-risk Non Muscle Invasive Bladder Cancer

Bladder Cancer Clinical Trial

— IMMUN VESSIE  

Official title:

Evaluation of PD-L1 Expression and Immune Infiltration in High-risk Non Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04726735
• Other study ID #: CHUBX2018/55
• Status: Completed
• Start date: March 16, 2020
• Est. completion date: May 14, 2020

Study information

• Verified date: January 2021
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence (60 to 70%) and progression (20 to 30%) to muscle-invasive bladder cancer (MIBC). The local immunotherapy (intra-vesical Bacillus Calmette-Guerin (BCG) following transurethral resection of the bladder tumor (TURBT)) reduces significantly the risk of recurrence and progression as compared to observation or to intra-vesical chemotherapy. Systemic immunotherapy with programmed death ligand-1 (PD-L1) or Programmed cell Death 1 (PD1) inhibitors has shown major efficacy in the treatment of patients with advanced/metastatic urothelial carcinoma who have progressed on platinum-based regimens of chemotherapy, or even in front line setting. In the field of NMIBC, immunotherapy using PD-L1 or PD1 inhibitors is under investigation but the frequency of PD-L1 expression has rarely been precisely described in the different subtypes. The aim of this retrospective study is to investigate the expression of PD-L1 by different types of NMIBC. The secondary objective is to characterize the immune contexture of NMIBC.

Description:

Non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence (60 to 70%) and progression (20 to 30%) to muscle-invasive bladder cancer (MIBC). The local immunotherapy (intra-vesical Bacillus Calmette-Guerin (BCG) following transurethral resection of the bladder tumor (TURBT)) reduces significantly the risk of recurrence and progression as compared to observation or to intra-vesical chemotherapy. Systemic immunotherapy with programmed death ligand-1 (PD-L1) or Programmed cell Death 1 (PD1) inhibitors has shown major efficacy in the treatment of patients with advanced/metastatic urothelial carcinoma who have progressed on platinum-based regimens of chemotherapy, or even in front line setting. In the field of NMIBC, immunotherapy using PD-L1 or PD1 inhibitors is under investigation but the frequency of PD-L1 expression has rarely been precisely described in the different subtypes. The aim of this retrospective study is to investigate the expression of PD-L1 by different types of NMIBC. The secondary objective is to characterize the immune contexture of NMIBC. The immunological contexture of NMIBC in comparison with normal bladder tissue and invasive bladder cancer will be deciphered. The objective is to determine immune signatures associated with response or relapse/progression, with and without immune treatments in NMIBC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 14, 2020
• Est. primary completion date: May 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Patients with histologically documented normal bladder, NMIBC (Ta, T1, CIS) or MIBC stored in the tissue bank. Samples collected from 2007 to 2011. 3 years follow-up is mandatory to assess the frequency of recurrences and progressions.

Exclusion Criteria:

• History of autoimmune disease
• Active tuberculosis
• Prior treatment with CD137 agonists, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Samples of bladder tissue
Samples of bladder tissue collected between 2007 and 2011.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Bordeaux	Talence

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Université de Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PD-L1 status (positive or negative) of the tumor and tumor associated immune cells.	PD-L1 status will be considered positive if more than 25% of tumor cells exhibit membrane staining or immune cells present (ICP) >1% and immune cells (IC)+ >25% or ICP=1% and IC+ = 100%.; PD-L1 status will be considered negative if none of the criteria for PD-L1 positive status are met.	Day 1
Secondary	Descriptive analysis of the differential expression of all the following immune biomarkers in normal bladder tissue, NMIBC (Non Muscle Invasive Bladder Cancer) and MIBC (Muscle Invasive Bladder Cancer).	Descriptive statistics will be performed from clinical characteristics as mean values for categorical variables, or medians (range) for non-normal continuous variables.	Day 1
Secondary	Association of immune profile with recurrence and progression rates	Association between all variables will be analysed with t-test, Mann Whitney or ANOVA multiple comparison test. Correlation analysis will be performed with ?2 and Fischer exact test. Results will be considered significant if the p-value is <0.05.	Day 1