Immune Microenvironment and Gene Expression Profiling in Mesothelioma
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorIstituto Oncologico Veneto IRCCS
About this trial
Pleural and peritoneal mesotheliomas (PPM) are rare cancers mostly related to asbestos-exposure, which are characterized by a complex histopathological diagnosis and staging, few therapeutic options and a dismal prognosis. The main unmet medical need in PPM is the lack of a treatment sequence for affected patients. The advent of immune checkpoint inhibitors has changed the first line treatment of PPM, thanks to the improvement in survival achieved by the combination of ipilimumab and nivolumab that are currently approved for non-epithelioid histology in our Country.
PPM is characterized by a large heterogeneity of the genomic landscape, which is mainly characterized by the loss of tumour suppressor genes and mutations in DNA repair genes and by an "altered- suppressed" or "excluded" tumor immune microenvironment (TIME).
The goal of this project is to improve the immune-biological and molecular stratification of PPM subgroups that can lead to the identification of different personalized treatment approaches. PPM patients (N=220) will be retrospectively (N=150) and prospectively (N=70) recruited from the coordinator center and 6 participating Italian centers. Treatment-naïve tumor samples will be collected and analyzed by bulk gene expression and spatial whole transcriptome analysis, and by 9-color multiplex immunofluorescence.
New targets or actionable pathways potentially emerging from such studies will be finally assessed and validated in patient-derived organoids/xenografts that accurately reflect PPM tumorigenesis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with Mesothelioma of the Pleura and Peritoneum
Age greater than 18 years of age
Patients undergoing surgery will require both biopsy and surgical sampling material
Pathologist's confirmation of the presence of tumor sections in the excised specimens
Disqualifiers
Inadequacy of biological material for analysis under study
Patients not amenable to active oncologic treatment
Patients lost to follow-up before 6 months after the end of active oncologic treatment
Trial population
220 PPM patients will be enrolled in 7 Centers, 150 retrospectively and 70 prospectively.
Trial design
Design model
Other
Time perspective
Other
Treatments tested in this trial
Translation analysis
Other interventionBulk GEP analysis, Spatial whole transcriptome analysis, mIF analysis of tumors
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Primary outcome
PPM treatment-naïve tumor samples and classification in different clusters according to the differential expression of molecular and gene signatures by Gene expression profile (GEP) analysis.
Time frame
Through study completion, an average of 3 years2
Primary outcome
Identification of molecular and immune signatures predictive of resistance or sensitivity to systemic anticancer drugs: chemotherapy or immunotherapy administered as first line treatment by spatial whole transcriptome analysis.
Time frame
Through study completion, an average of 3 years3
Primary outcome
PPM surgical specimens and comparison with GEP in matched treatment-naïve tumor samples will be performed by gene expression profile analysis with GEP analysis.
Time frame
Through study completion, an average of 3 yearsSecondary outcomes
1
Secondary outcome
Characterization and quantification of immune cell distribution and their spatial relationships in treatment naïve tumor samples of PPM patients will be performed by a 9-color multiplex immunofluorescence (mIF) analysis.
Time frame
Through study completion, an average of 3 years2
Secondary outcome
Immune phenotypes defined by mIF and the immune signatures identified by GEP analyses will be performed in each treatment-naïve tumor sample.
Time frame
Through study completion, an average of 3 yearsOther outcomes
1
Third outcome
In vitro and in vivo models of PPM for the investigation of activated signatures, new therapeutic targets and drug sensitivity tests. will be performed by: * development of in vitro 'organ-like' 3D structures (PDOs) derived from patient tumor tissue; * patient-derived xenograft (PDX) from PPM patients; * matched comparison of histological and molecular features of PDOs and PDXs with the original tumor tissues; * drug sensitivity/resistance tests in vitro and in vivo.
Time frame
Through study completion, an average of 3 yearsSponsors and contacts
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Source ClinicalTrials.gov