Immunmikromiljø og genuttrykksprofilering i mesothelioma (Imaging-Meso)
Fra immunmikromiljøkarakterisering og genekspresjonsprofilering til testing av nye medikamenter i pleural og peritoneal mesothelioma: Imaging-Meso-studie
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.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Kontakter og plasseringer
Studiesteder
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Alessandria, Italia, 15121
- Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
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Bergamo, Italia
- Asst Papa Giovanni Xxiii Bergamo
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Genova, Italia
- Ircss Ospedale Policlinico San Martino
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Milan, Italia
- Asst Grande Ospedale Metropolitano Niguarda-Milano
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Milan, Italia
- Fondazione Ircss Istituto Nazionale Dei Tumori Di Milano
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Padova, Italia, 35128
- Istituto Oncologico Veneto
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Parma, Italia, 43126
- Azienda Ospedaliera-Universitaria di Parma
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Verona, Italia
- Azienda Ospedaliera Universitaria Integrata Verona
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Milano
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Rozzano, Milano, Italia, 20089
- Istituto Clinico Humanitas
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Pordenone
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Aviano, Pordenone, Italia, 33081
- Centro di Riferimento Oncologico (CRO) IRCCS
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
220 PPM patients will be enrolled in 7 Centers, 150 retrospectively and 70 prospectively.
Beskrivelse
Inclusion Criteria:
- 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
- Patients in follow-up from active cancer treatment for at least 6 months
Exclusion Criteria:
- 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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Observasjonsmodeller: OTHER
- Tidsperspektiver: OTHER
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Primary outcome
Tidsramme: Through study completion, an average of 3 years
|
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
|
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Primary outcome
Tidsramme: Through study completion, an average of 3 years
|
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
Tidsramme: Through study completion, an average of 3 years
|
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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Secondary outcome
Tidsramme: Through study completion, an average of 3 years
|
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
Tidsramme: Through study completion, an average of 3 years
|
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
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Third outcome
Tidsramme: Through study completion, an average of 3 years
|
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:
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Through study completion, an average of 3 years
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Giulia Pasello, MD, Istituto Oncologico Veneto IOV IRCCS
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- Imaging-Meso study
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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