Ignite Creation Date:
2024-05-06 @ 8:20 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06341478
Status:
RECRUITING
Last Update Posted:
2024-04-02
First Post:
2024-03-19
Brief Title:
Investigator Grant IG 2022 27746
Sponsor:
IRCCS San Raffaele
Organization:
IRCCS San Raffaele
Study Overview
Official Title:
Understanding Tumor and Immune Dynamics and Predicting Response to Various Perioperative Therapies in Patients With Muscle-invasive Bladder Cancer
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Muscle-invasive bladder cancer MIBC is a systemic disease as 40 of patients pts ultimately develop recurrence after radical cystectomy RC For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy Single-agent pembrolizumab given neoadjuvantly in patients with T2-4N0M0 MIBC documented a 42 pathologic complete response-rate ypT0N0 in a previous AIRC-supported trial PURE-01 NCT02736266 PMID 30343614 However there is a huge proportion of pts who do not benefit from single-agent immunotherapy Antibody-drug conjugates ADC represent the next wave of MIBC treatment revolution An umbrella of various neoadjuvant therapies including the ADC Sacituzumab govitecan SG SG plus pembrolizumab and chemoimmunotherapy combination has been established to improve our knowledge on MIBC biology and to improve the outcomes
Hypothesis
By developing a robust biomarker program associated with therapeutic benefit of novel therapies or their combinations along with an imaging biomarker development the investigators will be able to identify suitable tumor characteristics for personalizing perioperative therapies in MIBC coupled with the possibility to predict the pathological response to treatment
Aims
The project is aimed at characterizing the tumor and microenvironment characteristics of muscle-invasive bladder cancer with a special focus on their changes induced by various neoadjuvant therapies preceding radical cystectomy
The investigators will aim to evaluate the tumor and immune profile on matched pre- vs post-therapy samples and noninvasively monitor the response to treatment with the use of radiological assessments
Experimental design
The investigators will access tumor samples from matched pre-therapy transurethral resection of the bladder tumor and post-therapy radical cystectomy surgical interventions They will also analyze the imaging analyses of combined bladder multiparametric MRIFluorodeoxyglucose Positron Emission Tomography PET scans pre-post neoadjuvant therapies and will associate the data with the pathological response to treatment expanding our previously reported work PMID 31882281
Biomarker analyses will include the following i multiplex immunofluorescence assays will allow the investigators defining the immune contexture of tumor lesion ii multiparametric flow cytometry will allow the phenotypic and functional analysis of peripheral blood cells at single cell level iii a whole transcriptome assay will enable investigators to assign specific molecular subtypes to pathological response and outcome as previously reported PMID 33785257 32165065
Expected results
The investigators will expect to identify the tumor characteristics and immune-profiling enabling them to delineate the selection of patients most suited for certain novel perioperative therapies thus anticipating the developments in clinical research that are being conducted worldwide in MIBC
The investigators will be also able to develop noninvasive tools for pathological complete response identification thus enabling them to develop a next-generation of clinical trials aimed at sparing any radical local therapy on the bladder tumor
Impact on cancer
In principle the present personalized strategy yields the potential to enhance the therapeutic standards achievable with RC alone as well as with single-agent immunotherapy and RC
Muscle-invasive bladder cancer MIBC is a systemic disease as 40 of patients pts ultimately develop recurrence after radical cystectomy RC For pts who cannot receive or refuse cisplatin-based chemotherapy there is no standard-of-care neoadjuvant therapy Single-agent pembrolizumab given neoadjuvantly in patients with T2-4N0M0 MIBC documented a 42 pathologic complete response-rate ypT0N0 in a previous AIRC-supported trial PURE-01 NCT02736266 PMID 30343614 However there is a huge proportion of pts who do not benefit from single-agent immunotherapy Antibody-drug conjugates ADC represent the next wave of MIBC treatment revolution An umbrella of various neoadjuvant therapies including the ADC Sacituzumab govitecan SG SG plus pembrolizumab and chemoimmunotherapy combination has been established to improve our knowledge on MIBC biology and to improve the outcomes
Hypothesis
By developing a robust biomarker program associated with therapeutic benefit of novel therapies or their combinations along with an imaging biomarker development the investigators will be able to identify suitable tumor characteristics for personalizing perioperative therapies in MIBC coupled with the possibility to predict the pathological response to treatment
Aims
The project is aimed at characterizing the tumor and microenvironment characteristics of muscle-invasive bladder cancer with a special focus on their changes induced by various neoadjuvant therapies preceding radical cystectomy
The investigators will aim to evaluate the tumor and immune profile on matched pre- vs post-therapy samples and noninvasively monitor the response to treatment with the use of radiological assessments
Experimental design
The investigators will access tumor samples from matched pre-therapy transurethral resection of the bladder tumor and post-therapy radical cystectomy surgical interventions They will also analyze the imaging analyses of combined bladder multiparametric MRIFluorodeoxyglucose Positron Emission Tomography PET scans pre-post neoadjuvant therapies and will associate the data with the pathological response to treatment expanding our previously reported work PMID 31882281
Biomarker analyses will include the following i multiplex immunofluorescence assays will allow the investigators defining the immune contexture of tumor lesion ii multiparametric flow cytometry will allow the phenotypic and functional analysis of peripheral blood cells at single cell level iii a whole transcriptome assay will enable investigators to assign specific molecular subtypes to pathological response and outcome as previously reported PMID 33785257 32165065
Expected results
The investigators will expect to identify the tumor characteristics and immune-profiling enabling them to delineate the selection of patients most suited for certain novel perioperative therapies thus anticipating the developments in clinical research that are being conducted worldwide in MIBC
The investigators will be also able to develop noninvasive tools for pathological complete response identification thus enabling them to develop a next-generation of clinical trials aimed at sparing any radical local therapy on the bladder tumor
Impact on cancer
In principle the present personalized strategy yields the potential to enhance the therapeutic standards achievable with RC alone as well as with single-agent immunotherapy and RC
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None