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Multidimensional Omics Analysis in Malignant Pleural Mesothelioma (OMIM)

24. april 2026 oppdatert av: 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.

Studieoversikt

Status

Rekruttering

Forhold

Ondartet pleural mesothelioma (MPM)

Detaljert beskrivelse

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

Observasjonsmessig

Registrering (Antatt)

300

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Navn: Alessia Ciarrocchi, PhD
Telefonnummer: 0522/295668
E-post: alessia.ciarrocchi@ausl.re.it

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

Voksen
Eldre voksen

Tar imot friske frivillige

Nei

Prøvetakingsmetode

Sannsynlighetsprøve

Studiepopulasjon

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.

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Antall grupper / kohorter

Kohorter og intervensjoner

Gruppe / Kohort
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.

Hva måler studien?

Primære resultatmål

Resultatmål	Tiltaksbeskrivelse	Tidsramme
High-resolution mapping of the organization of the tumor-infiltrating immune system in MPM Tidsramme: 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

Sekundære resultatmål

Resultatmål	Tidsramme
Immune-related gene signatures by whole transcriptome sequencing (normalized counts). Tidsramme: 36 months	36 months
Immune-phenotyping by multiple parametric cytofluorimetry (cell counts) Tidsramme: 36 months	36 months
Analysis of circulating cytokines by bead-based multiplex assays (concentration micrograms/microliter) Tidsramme: 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) Tidsramme: 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) Tidsramme: 36 months	36 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Azienda USL Reggio Emilia - IRCCS

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

30. august 2024

Primær fullføring (Faktiske)

30. august 2024

Studiet fullført (Antatt)

28. februar 2027

Datoer for studieregistrering

Først innsendt

16. april 2026

Først innsendt som oppfylte QC-kriteriene

24. april 2026

Først lagt ut (Faktiske)

1. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)