Ignite Creation Date:
2024-05-06 @ 10:36 AM
Last Modification Date:
2024-10-26 @ 12:32 PM
Study NCT ID:
NCT03303885
Status:
COMPLETED
Last Update Posted:
2020-10-19
First Post:
2017-10-03
Brief Title:
The FGFFGFR Signalling Pathway
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Centre Hospitalier Universitaire de Nice
Study Overview
Official Title:
The FGFFGFR Signalling Pathway a Novel Therapeutic Target in Liposarcomas
Status:
COMPLETED
Status Verified Date:
2020-10
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:
FILIPO
Brief Summary:
Liposarcomas are the most common type of soft tissue sarcomas STS Among liposarcomas well-differentiated liposarcoma WDLPSdedifferentiated liposarcoma DDLPS are the most frequent types WDLPS are composed mostly of mature fat whereas DDLPS contain both a WDLPS component and a non-lipomatous sarcoma component mostly of high grade More than 50 of DDLPS will relapse locally A significant proportion of patients will remain with a non-resectable disease that will metastasize in 20 of cases Standard chemotherapy is poorly efficient and alternative options are so far limited Identification of new therapeutic targets is urgent and mandatory the recent preliminary results as well as data from the literature led us to hypothesize that the FGF Fibroblast Growth factorFGFR pathway is involved in liposarcomagenesis and might therefore be a novel relevant therapeutic target in WDLPSDDLPS
Description of the project The project associates 4 teams with a longstanding collaboration 3 teams fom Nice Nice University HospitalIRCAN Nice University Hospital Comprehensive Cancer Center Centre Antoine Lacassagne and one team from Bordeaux Comprehensive Cancer Center Institut Bergonié These 4 teams are experts in the clinics pathology and molecular genetics of sarcomas as well as in biostatistics
1 Expression studies on the role of the syndecan-1 SDC1FGFR pathway in WDLPSDDLPS tumorigenesis
The recent studies provide original results that may have a direct application in treatments of liposarcomas They suggest that SDC1 -an effector of the FGFFGFR pathway- might be involved in DDLPS tumorigenesis Staff will analyse
The pattern of expression and localisation of syndecans FGFs and FGFRs in WDLPSDDLPS both in a large collection of 249 primary tumors and in our in-house panel of high quality and validated human WDLPSDDLPS cell lines
The prognostic value of SDC1 FGF2 and FGF18 expression by correlation to the patient clinical outcomes
2 Fonctional studies of the role of the SDC1FGFR pathway in WDLPSDDLPS tumorigenesis We will analyse
The effects of modulating SDC1 FGFR expression in WDLPS and DDLPS cells on cell proliferation cell cycle apoptosis and on their capacity to differentiate in adipocytes
The sensitivity of WDLPS and DDLPS cells to the FGFR inhibitor JNJ-427556493 as a single agent or in combination with other antagonists
The mechanisms of sensitivity and resistance to JNJ-427556493 by phosphoproteomic analysis of WDLPS and DDLPS cells before and after JNJ-427556493 treatment
The involvement of SDC1 in the dedifferentiation process of liposarcoma Expected results staff expect to demonstrate the relevance of the SDC1FGFR pathway in liposarcomas We also expect to link drug activity to genomics and proteomics data This will allow the characterization of the activity of FGFR inhibitors and the identification of powerful preclinical biomarkers of drug activity and mechanisms of resistance in DDLPS The availability of xenograft models will allow us to validate our in vitro findings in the in vivo setting with the ultimate goal to improve patient management
The availability of an early clinical trial unit in Institut Bergonié managed by A Italiano will give the immediate opportunity to transfer our data to the management of metastatic liposarcoma patients
Description of the project The project associates 4 teams with a longstanding collaboration 3 teams fom Nice Nice University HospitalIRCAN Nice University Hospital Comprehensive Cancer Center Centre Antoine Lacassagne and one team from Bordeaux Comprehensive Cancer Center Institut Bergonié These 4 teams are experts in the clinics pathology and molecular genetics of sarcomas as well as in biostatistics
1 Expression studies on the role of the syndecan-1 SDC1FGFR pathway in WDLPSDDLPS tumorigenesis
The recent studies provide original results that may have a direct application in treatments of liposarcomas They suggest that SDC1 -an effector of the FGFFGFR pathway- might be involved in DDLPS tumorigenesis Staff will analyse
The pattern of expression and localisation of syndecans FGFs and FGFRs in WDLPSDDLPS both in a large collection of 249 primary tumors and in our in-house panel of high quality and validated human WDLPSDDLPS cell lines
The prognostic value of SDC1 FGF2 and FGF18 expression by correlation to the patient clinical outcomes
2 Fonctional studies of the role of the SDC1FGFR pathway in WDLPSDDLPS tumorigenesis We will analyse
The effects of modulating SDC1 FGFR expression in WDLPS and DDLPS cells on cell proliferation cell cycle apoptosis and on their capacity to differentiate in adipocytes
The sensitivity of WDLPS and DDLPS cells to the FGFR inhibitor JNJ-427556493 as a single agent or in combination with other antagonists
The mechanisms of sensitivity and resistance to JNJ-427556493 by phosphoproteomic analysis of WDLPS and DDLPS cells before and after JNJ-427556493 treatment
The involvement of SDC1 in the dedifferentiation process of liposarcoma Expected results staff expect to demonstrate the relevance of the SDC1FGFR pathway in liposarcomas We also expect to link drug activity to genomics and proteomics data This will allow the characterization of the activity of FGFR inhibitors and the identification of powerful preclinical biomarkers of drug activity and mechanisms of resistance in DDLPS The availability of xenograft models will allow us to validate our in vitro findings in the in vivo setting with the ultimate goal to improve patient management
The availability of an early clinical trial unit in Institut Bergonié managed by A Italiano will give the immediate opportunity to transfer our data to the management of metastatic liposarcoma patients
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
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