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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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Translation analysis | Other | Bulk GEP analysis, Spatial whole transcriptome analysis, mIF analysis of tumors |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Through study completion, an average of 3 years |
| 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. | Through study completion, an average of 3 years |
| 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. | Through study completion, an average of 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Through study completion, an average of 3 years |
| Secondary outcome |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
|
Inclusion Criteria:
Exclusion Criteria:
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220 PPM patients will be enrolled in 7 Centers, 150 retrospectively and 70 prospectively.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Giulia Pasello, MD | Contact | 0498215608 | giulia.pasello@iov.veneto.it | |
| Gian Luca De Salvo, MD | Contact | 0498215704 | clinical.trial@iov.veneto.it |
| Name | Affiliation | Role |
|---|---|---|
| Giulia Pasello, MD | Istituto Oncologico Veneto IOV IRCCS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Istituto Clinico Humanitas | Recruiting | Rozzano | Milano | 20089 | Italy |
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| ID | Term |
|---|---|
| D008654 | Mesothelioma |
| D000086002 | Mesothelioma, Malignant |
| ID | Term |
|---|---|
| D000236 | Adenoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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tumor tissue
Immune phenotypes defined by mIF and the immune signatures identified by GEP analyses will be performed in each treatment-naïve tumor sample. |
| Through study completion, an average of 3 years |
| Through study completion, an average of 3 years |
| Centro di Riferimento Oncologico (CRO) IRCCS | Recruiting | Aviano | Pordenone | 33081 | Italy |
|
| Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo | Recruiting | Alessandria | 15121 | Italy |
|
| Asst Papa Giovanni Xxiii Bergamo | Recruiting | Bergamo | Italy |
|
| Ircss Ospedale Policlinico San Martino | Recruiting | Genova | Italy |
|
| Asst Grande Ospedale Metropolitano Niguarda-Milano | Recruiting | Milan | Italy |
|
| Fondazione Ircss Istituto Nazionale Dei Tumori Di Milano | Recruiting | Milan | Italy |
|
| Istituto Oncologico Veneto | Recruiting | Padova | 35128 | Italy |
|
| Azienda Ospedaliera-Universitaria di Parma | Recruiting | Parma | 43126 | Italy |
|
| Azienda Ospedaliera Universitaria Integrata Verona | Recruiting | Verona | Italy |
|
| D018301 |
| Neoplasms, Mesothelial |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D010997 | Pleural Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |