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Multidimensional Omics Analysis in Malignant Pleural Mesothelioma (OMIM)

24 april 2026 bijgewerkt door: Azienda USL Reggio Emilia - IRCCS

Multidimensional Omics and Functional Approaches to Improve Immunotherapy Efficacy in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and incurable cancer. Most patients are diagnosed with unresectable disease for which treatment options are limited. The lack of prognostic biomarkers further complicates the decision-making. Recently, the introduction of immune checkpoint inhibitors (ICIs) has marked a shift but has failed to produce significant benefits for a large proportion of patients. Maximizing the efficiency of ICIs and developing new protocols to improve drug efficacy is the best possible strategy for improving the life expectancy and quality of life of patients with MPM. This study aims to characterize the organization of the immune system infiltrating mesothelioma and the dynamics of its interaction with the tumor. The rationale is that deciphering this complexity will help improve our understanding of the mechanisms underlying this disease and provide a new tool to optimize the use of ICIs in these patients.

Studie Overzicht

Toestand

Werving

Conditie

Kwaadaardig pleuraal mesothelioom (MPM)

Gedetailleerde beschrijving

Malignant Pleural Mesothelioma (MPM) is a rare and highly aggressive malignancy characterized by poor prognosis and limited therapeutic options. Most patients are diagnosed at an advanced, unresectable stage, with a median overall survival of approximately one year. Although the introduction of immune checkpoint inhibitors (ICIs) has represented a significant advancement, a substantial proportion of patients fail to derive meaningful clinical benefit. The lack of reliable prognostic and predictive biomarkers, together with marked molecular heterogeneity and limited understanding of disease biology, significantly hampers the development of effective therapeutic strategies. MPM is strongly associated with chronic inflammation driven by asbestos exposure, which profoundly alters the pleural microenvironment. Within this context, tumor cells and immune cells engage in dynamic and reciprocal interactions, generating a complex ecosystem that promotes disease progression and the emergence of aggressive phenotypes. The ability of tumor cells to modulate immune system activity is considered a key driver of MPM pathogenesis. This study aims to comprehensively characterize the organization of the tumor-infiltrating immune system and the dynamic interactions between tumor and immune cells. To achieve this goal, an integrative and multidimensional omics approach will be employed to generate a high-resolution map of MPM ecosystem and to identify novel biomarkers and potential therapeutic targets. This is an exploratory, non-interventional, non-pharmacological study with both prospective and retrospective components, conducted exclusively on biological samples collected during routine clinical practice. The study population will be structured into three complementary cohorts. A training prospective cohort (C1 - Training Set) including newly diagnosed MPM patients from whom fresh frozen (FF) tumor samples will be collected from diagnostic biopsies, surgical resections, or malignant pleural effusions, enabling in-depth characterization of the tumor and immune microenvironment. A validation independent retrospective cohort (C2 - Validation Set) including MPM samples collected between 2015 and 2022 and used to validate findings obtained in the training cohort. A nested cohort within C1 (C3 - HITHOC Set) that will include patients undergoing surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC), allowing investigation of tumor-immune interactions and treatment response mechanisms in this specific clinical setting. By integrating data across these three cohorts, the study aims to identify immune-related markers associated with tumor aggressiveness, discover novel targets for next-generation immunotherapies, and characterize mechanisms underlying response to chemotherapy, with particular focus on the HITHOC setting. Expected outcomes include improved understanding of MPM biology, identification of novel biomarkers, and optimization of immunotherapy strategies, ultimately contributing to the development of more effective and personalized treatments for patients affected by this disease.

Studietype

Observationeel

Inschrijving (Geschat)

300

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Naam: Alessia Ciarrocchi, PhD
Telefoonnummer: 0522/295668
E-mail: alessia.ciarrocchi@ausl.re.it

Studie Locaties

Italië
- - Catania, Italië
    - Werving
    - Azienda Ospedaliera Universitaria Policlinico Rodolico San Marco di Catania
    - Contact:
      
      Giacomo Cusumano, MD PhD
      
      Telefoonnummer: 095 3781175
      
      E-mail: giacomo.cusumano@unict.it
  - Naples, Italië
    - Werving
    - Azienda Ospedaliera Universitaria Luigi Vanvitelli, Napoli
    - Contact:
      
      Alfonso Fiorelli, MD PhD
      
      E-mail: alfonso.fiorelli@unicampania.it
  - Reggio Emilia, Italië
    - Werving
    - Azienda USL IRCCS di Reggio Emilia
    - Contact:
      
      Alessia Ciarrocchi, PhD
      
      Telefoonnummer: 0522/295668
      
      E-mail: alessia.ciarrocchi@ausl.re.it
    - Hoofdonderzoeker:
      
      Alessia Ciarrocchi, PhD
  - Roma, Italië
    - Werving
    - Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    - Contact:
      
      Filippo Lococo, MD
      
      Telefoonnummer: 06 8881 8881
      
      E-mail: filippo.lococo@policlinicogemelli.it

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

Volwassen
Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

The study population includes patients diagnosed with Malignant Pleural Mesothelioma (MPM). Both prospective and retrospective cohorts will be included to ensure a comprehensive and biologically representative characterization of the disease. Eligible patients will have histologically confirmed MPM and available tumor biological samples obtained from diagnostic biopsies, surgical resections, or pleural effusions. Samples will include both fresh frozen (FF) material and formalin-fixed paraffin-embedded (FFPE) archival specimens.

Beschrijving

Inclusion Criteria:

Participant is willing and able to give informed consent for participation in the study
Aged > 18 years
Patients with histologically confirmed diagnosis of MPM
Availability of biological material
Clinical indicatio of eligibility for HITOCH protocol (only for C3 cohort)

Exclusion Criteria:

Active current infection
Autoimmune disease
Women in childbearing age not able to exclude pregnancy

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Aantal groepen / cohorten

Cohorten en interventies

Groep / Cohort
C1 - Training set A prospective cohort of MPM patients enrolled. Analyses will be performed on fresh frozen (FF) tumor samples derived from diagnostic biopsies, surgical resections, or malignant pleural effusions (MPE).
C2 - Validation Set An independent retrospective cohort of MPM samples collected between 2015 and 2022. This cohort will serve to validate findings obtained in the training set.
C3 - HITHOC Set An prospective cohort of patients undergoing surgery combined with hyperthermic intrathoracic chemotherapy (HITHOC). This cohort will enable investigation of tumor-immune interactions and treatment response mechanisms in this specific clinical setting.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
High-resolution mapping of the organization of the tumor-infiltrating immune system in MPM Tijdsspanne: 36 months	Characterization of the composition, functional state, and spatial organization of tumor-infiltrating immune cells using integrated bulk, single-cell, and spatial transcriptomic analyses on tumor tissues and malignant pleural effusions.	36 months

Secundaire uitkomstmaten

Uitkomstmaat	Tijdsspanne
Immune-related gene signatures by whole transcriptome sequencing (normalized counts). Tijdsspanne: 36 months	36 months
Immune-phenotyping by multiple parametric cytofluorimetry (cell counts) Tijdsspanne: 36 months	36 months
Analysis of circulating cytokines by bead-based multiplex assays (concentration micrograms/microliter) Tijdsspanne: 36 months	36 months
Association between immune features and clinical outcomes by correlation between gene expression (normalized, cell counts and/or concentration counts) and overall survival (months) Tijdsspanne: 36 months	36 months
Association between transcriptional signatures and pathological response to chemotherapy by correlation of gene expression (normalized counts) and response to therapy (time to progression -months) Tijdsspanne: 36 months	36 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Azienda USL Reggio Emilia - IRCCS

Onderzoekers

Hoofdonderzoeker: Alessia Ciarrocchi, Azienda USL - IRCCS di Reggio Emilia

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

30 augustus 2024

Primaire voltooiing (Werkelijk)

30 augustus 2024

Studie voltooiing (Geschat)

28 februari 2027

Studieregistratiedata

Eerst ingediend

16 april 2026

Eerst ingediend dat voldeed aan de QC-criteria

24 april 2026

Eerst geplaatst (Werkelijk)

1 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)