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MesotheliomaNCT06536179

New Preclinical and Clinical Approaches to Mesothelioma

An observational study of Mesothelioma, run by Marco Emilio Bianchi at 2 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study protocol involves the coordination between UO1 (IRCCS San Raffaele Hospital) and UO2 (Istituto Nazionale Tumori di Napoli - IRCCS G. Pascale) to explore the role of HMGB1 and CXCR4 in cancer treatment and metastasis. Read more about this study

Who is it for?
Any age
Conditions the study is for
Mesothelioma
How many people
70 participants
Where
2 sitesItaly
Study dates
25 Jul 2024to 25 Jan 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: For this study, San Raffaele Hospital and Istituto Nazionale Tumori IRCCS Fondazione G. Pascale will enroll both: * patients with a clinical suspicion of mesothelioma (cancer patients), and for which surgery is indicated and will be performed as per clinical practice. From the biopsies thus obtained in accordance with normal clinical practice (the biopsies provided to us by the clinic are considered waste material) whose biopsies mesothelioma organoids will be obtained; * patients with a clinical suspicion or diagnosis different from that of mesothelioma, from whose biopsies (the biopsies provided to us by the clinic are considered waste material) non-tumoral organoids will be obtained to serve as controls for the tumoral ones.

Who may be able to join

  • Patients with Mesothelioma:
  • Clinical suspicion or histologically confirmed diagnosis of pleural mesothelioma.
  • Candidates for surgical intervention.
  • Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well as breastfeeding women.
  • Capacity to comprehend the study nature and provide autonomously informed consent.
  • Control Group patients:
Show all 11Show fewer
  • Absence of pleural mesothelioma but presence of other histologically confirmed diseases (neoplastic, inflammatory, or infectious).
  • Candidates for surgical intervention.
  • Age 18 years or older. It is possible to include both male and female patients, male and female patients of reproductive age, as well breastfeeding women.
  • Ability to understand the study nature and provide autonomously informed consent.
  • If the patient's diagnosis, whether provisional or definitive, does not confirm the clinical suspicion, they will not undergo further evaluation in the study.

Who cannot join

  • Lack of biopsy material.
  • pregnancy.
  • Unwillingness to sign the Informed Consent.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Massimo Crippa, PhD contact

02-26434833

crippa.massimo@hsr.it

Italy2 sites, 2 recruiting

  • IRCCS San Raffaele

    Milan, Lombardy, 20132

    Bianchi Marco, Professor, 2-26434765, bianchi.marco@hsr.it

    Giovanna Musco, PhD

    Recruiting

  • Istituto Nazionale Tumori IRCCS Fondazione G.Pascale

    Naples, Campania, 80131

    Vincenzo Sforza, MD, 081-17770705, v.sforza@istitutotumori.na.it

    Vincenzo Sforza, MD

    Recruiting

Other trials in Italy

About this study

Official title: New Preclinical and Clinical Approaches to Mesothelioma, an Archetypal Inflammatory Tumor

This study protocol involves the coordination between UO1 (IRCCS San Raffaele Hospital) and UO2 (Istituto Nazionale Tumori di Napoli - IRCCS G. Pascale) to explore the role of HMGB1 and CXCR4 in cancer treatment and metastasis. UO1 focuses on the role of HMGB1 in inflammation, mesothelioma progression, and tissue repair, as well as developing, in future, possible HMGB1 inhibitors for cancer therapy. UO2 specializes in CXCR4's role in cancer, developing CXCR4 antagonists, and tracking CXCR4-dependent metastasis. The hypothesis is that targeting HMGB1 and CXCR4 pathways will inhibit tumor progression and metastasis, enhancing anti-tumor immunity and improving therapeutic outcomes in cancer.

Read the detailed description

This is a multicentric cross-sectional observational study with an additional blood volume collected during blood sampling performed for normal clinical practice. The enrollment will take

Conditions
Mesothelioma
Medical subject headings
Mesothelioma

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To set up spheroids models to study and serve as a platform

    Number of spheroids with infiltrated macrophages. About of 30% of macrophages infiltrated into spheroids.

    Measured: 0/baseline

  2. To set up spheroids models and serve as a platform

    Evaluation of macrophages polarization status M1 or M2 based on different genes and proteins expression using qPCR and Flow Cytometry.

    Measured: 0/baseline

  3. To set up organoid models

    Number of organoids formation. About of 30% of biopsies generated organoids.

    Measured: 0/baseline

  4. Test inhibitors on spheroids and organoids and assess the response of individual patients to therapy

    Rate of growth to test the efficacy of anti-CSF1R, BoxA and DFL using human mesospheres from MPM primary cell lines derived from patients and monocytes from controls.

    Measured: 0/baseline

Secondary outcomes (3)

  1. To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

    Percentage of migrated or invaded MPM cell lines NCI-H2052 (BAP1 WT/NF2 MUT) vs NCI-H28 (BAP1 mut/NF2 WT) with and without macrophages in presence of CDDP-Nivolumab (NIVO)-Peptide R54.

    Measured: 0/baseline

  2. To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

    Percentage of cell death of Tregs/Macrophages from peripheral blood and pleural effusion derived from MPM patients treated with and without R54.

    Measured: 0/baseline

  3. To investigate inhibitors of the CXCR4-CXCL12-HMGB1 axis on the crosstalk

    Overall survival of mice with MPM treated with CDDP-anti-PD-1/R54.

    Measured: In vivo experiment 3 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2024
  2. Study start25 Jul 2024
  3. Primary completion25 Jul 2025 (estimated)
  4. Study completion25 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Other
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06536179
Sponsor's protocol ID
PNRR-TR1-2023-12377199
Status last verified
Jul 2024
First submitted
26 Jul 2024
Last updated
2 Aug 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Shimizu Y, Dobashi K, Imai H, Sunaga N, Ono A, Sano T, Hikino T, Shimizu K, Tanaka S, Ishizuka T, Utsugi M, Mori M. CXCR4+FOXP3+CD25+ lymphocytes accumulate in CXCL12-expressing malignant pleural mesothelioma. Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):43-51. doi: 10.1177/039463200902200106.

    PubMed 19309551

  • Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Rovere Querini P, Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev. 2017 Nov;280(1):74-82. doi: 10.1111/imr.12601.

    PubMed 29027228

  • Santagata S, Napolitano M, D'Alterio C, Desicato S, Maro SD, Marinelli L, Fragale A, Buoncervello M, Persico F, Gabriele L, Novellino E, Longo N, Pignata S, Perdona S, Scala S. Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer. Oncotarget. 2017 Aug 19;8(44):77110-77120. doi: 10.18632/oncotarget.20363. eCollection 2017 Sep 29.

    PubMed 29100374

  • Li B, Zeng Y, Reeves PM, Ran C, Liu Q, Qu X, Liang Y, Liu Z, Yuan J, Leblanc PR, Ye Z, Sluder AE, Gelfand JA, Brauns TA, Chen H, Poznansky MC. AMD3100 Augments the Efficacy of Mesothelin-Targeted, Immune-Activating VIC-008 in Mesothelioma by Modulating Intratumoral Immunosuppression. Cancer Immunol Res. 2018 May;6(5):539-551. doi: 10.1158/2326-6066.CIR-17-0530. Epub 2018 Mar 6.

    PubMed 29511032

  • Kinoshita Y, Hamasaki M, Yoshimura M, Matsumoto S, Iwasaki A, Nabeshima K. Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma. Mod Pathol. 2020 Feb;33(2):235-244. doi: 10.1038/s41379-019-0309-6. Epub 2019 Jun 23.

    PubMed 31231129

  • D'Alterio C, Buoncervello M, Ierano C, Napolitano M, Portella L, Rea G, Barbieri A, Luciano A, Scognamiglio G, Tatangelo F, Anniciello AM, Monaco M, Cavalcanti E, Maiolino P, Romagnoli G, Arra C, Botti G, Gabriele L, Scala S. Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the tumor microenvironment and inhibiting neoplastic PD-1. J Exp Clin Cancer Res. 2019 Oct 28;38(1):432. doi: 10.1186/s13046-019-1420-8.

    PubMed 31661001

  • Zhang M, Luo JL, Sun Q, Harber J, Dawson AG, Nakas A, Busacca S, Sharkey AJ, Waller D, Sheaff MT, Richards C, Wells-Jordan P, Gaba A, Poile C, Baitei EY, Bzura A, Dzialo J, Jama M, Le Quesne J, Bajaj A, Martinson L, Shaw JA, Pritchard C, Kamata T, Kuse N, Brannan L, De Philip Zhang P, Yang H, Griffiths G, Wilson G, Swanton C, Dudbridge F, Hollox EJ, Fennell DA. Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment. Nat Commun. 2021 Mar 19;12(1):1751. doi: 10.1038/s41467-021-21798-w.

    PubMed 33741915

  • Bertolini G, Cancila V, Milione M, Lo Russo G, Fortunato O, Zaffaroni N, Tortoreto M, Centonze G, Chiodoni C, Facchinetti F, Pollaci G, Taie G, Giovinazzo F, Moro M, Camisaschi C, De Toma A, D'Alterio C, Pastorino U, Tripodo C, Scala S, Sozzi G, Roz L. A novel CXCR4 antagonist counteracts paradoxical generation of cisplatin-induced pro-metastatic niches in lung cancer. Mol Ther. 2021 Oct 6;29(10):2963-2978. doi: 10.1016/j.ymthe.2021.05.014. Epub 2021 May 21.

    PubMed 34023505

  • Oien DB, Sarkar Bhattacharya S, Chien J, Molina J, Shridhar V. Quinacrine Has Preferential Anticancer Effects on Mesothelioma Cells With Inactivating NF2 Mutations. Front Pharmacol. 2021 Sep 21;12:750352. doi: 10.3389/fphar.2021.750352. eCollection 2021.

    PubMed 34621176

  • Santagata S, Rea G, Castaldo D, Napolitano M, Capiluongo A, D'Alterio C, Trotta AM, Ierano C, Portella L, Di Maro S, Tatangelo F, Albino V, Guarino R, Cutolo C, Izzo F, Scala S. Hepatocellular carcinoma (HCC) tumor microenvironment is more suppressive than colorectal cancer liver metastasis (CRLM) tumor microenvironment. Hepatol Int. 2024 Apr;18(2):568-581. doi: 10.1007/s12072-023-10537-6. Epub 2023 May 4.

    PubMed 37142825

  • Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, Borczuk AC, Butnor K, Cagle PT, Chirieac LR, Churg A, Dacic S, Fraire A, Galateau-Salle F, Gibbs A, Gown A, Hammar S, Litzky L, Marchevsky AM, Nicholson AG, Roggli V, Travis WD, Wick M; International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013 May;137(5):647-67. doi: 10.5858/arpa.2012-0214-OA. Epub 2012 Aug 28.

    PubMed 22929121

Questions about this trial

What is this clinical trial studying?

An observational study of Mesothelioma, run by Marco Emilio Bianchi at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Massimo Crippa, PhD (02-26434833, crippa.massimo@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To set up spheroids models to study and serve as a platform (time frame: 0/baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06536179, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.

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