- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03303885
The FGF/FGFR Signalling Pathway: (FILIPO)
The FGF/FGFR Signalling Pathway: a Novel Therapeutic Target in Liposarcomas
Liposarcomas are the most common type of soft tissue sarcomas (STS). Among liposarcomas, well-differentiated liposarcoma (WDLPS)/dedifferentiated 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 factor)/FGFR pathway is involved in liposarcomagenesis and might therefore be a novel relevant therapeutic target in WDLPS/DDLPS.
Description of the project The project associates 4 teams with a longstanding collaboration : 3 teams fom Nice (Nice University Hospital/IRCAN, 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.
Expression studies on the role of the syndecan-1 (SDC1)/FGFR pathway in WDLPS/DDLPS 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 FGF/FGFR pathway- might be involved in DDLPS tumorigenesis. Staff will analyse:
- The pattern of expression and localisation of syndecans, FGFs and FGFRs in WDLPS/DDLPS both in a large collection of 249 primary tumors and in our in-house panel of high quality and validated human WDLPS/DDLPS cell lines.
- The prognostic value of SDC1, FGF2 and FGF18 expression by correlation to the patient clinical outcomes
Fonctional studies of the role of the SDC1/FGFR pathway in WDLPS/DDLPS 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 SDC1/FGFR 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.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Nice, France, 06000
- Nice hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- A biopsy and\or an exérèse with diagnostic or curative aim will have been practised within the framework of a well differentiated liposarcome or dédifférencié with development of the gene MDM2
- A taking of the tumor is available (frozen fragment and\or block fixed in paraffin wax) - not opposition of the patient will have been looked for
Exclusion Criteria:
Liposarcome not differentiated
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Cross-Sectional
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
difference in terms of overall survival: between FGF18 - versus FGF18+
Time Frame: 24 months
|
overall survival, recurrence
|
24 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16-PRTK
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Liposarcoma
-
Mario Negri Institute for Pharmacological ResearchFondazione IRCCS Istituto Nazionale dei Tumori, Milano; Humanitas Hospital,...RecruitingLiposarcoma, Myxoid | Liposarcoma, Dedifferentiated | Liposarcoma, Round CellItaly
-
GlaxoSmithKlineCompleted
-
Johnson & Johnson Pharmaceutical Research & Development...PharmaMarCompletedLiposarcoma,MyxoidFrance, United States, Germany
-
Memorial Sloan Kettering Cancer CenterRecruitingSarcoma | Soft Tissue Sarcoma | Sarcoma,Soft Tissue | Dedifferentiated Liposarcoma | Recurrent Dedifferentiated Liposarcoma | Metastatic Dedifferentiated Liposarcoma | Unresectable Dedifferentiated LiposarcomaUnited States
-
The Netherlands Cancer InstituteUnknownMyxoid Liposarcoma of Soft TissueNetherlands, United Kingdom, Norway, United States, Denmark
-
Maria Sklodowska-Curie National Research Institute...Active, not recruiting
-
The Netherlands Cancer InstituteM.D. Anderson Cancer Center; Mayo Clinic; Radboud University Medical Center; Aarhus... and other collaboratorsRecruitingMyxoid LiposarcomaNetherlands
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI); Daiichi Sankyo, Inc.Completed
-
Systems Medicine LLCUnknown
-
Sarcoma Alliance for Research through CollaborationEli Lilly and CompanyRecruitingAdvanced Dedifferentiated LiposarcomaUnited States