Biomarker Validation Tests for Mesothelioma

Overseen By Raphael Bueno

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Unsuitable for surgery, treatment, diagnosis

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to understanding the stage and outlook of malignant pleural mesothelioma, a cancer affecting the lung lining. Researchers are testing two methods, the CLDN15/VIM Test (Claudin-15/Vimentin Test) and the MPT Test, to evaluate their effectiveness in identifying the cancer's status. Suitable candidates for this trial have been diagnosed with malignant pleural mesothelioma and are undergoing a procedure to collect tissue samples from the lung area. As an unphased trial, this study provides patients with a unique opportunity to contribute to groundbreaking research that could enhance future diagnostic methods.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this method is safe for determining stage and prognosis of mesothelioma?

Research has shown that the CLDN15/VIM test and the MPT test are being studied to assess their effectiveness in determining the stage and prognosis for individuals with malignant pleural mesothelioma. These tests examine gene expression, analyzing how certain genes function in the body.

While there is limited direct information on the safety of these specific tests, they generally involve analyzing tissue samples and are considered safe. The CLDN15/VIM test measures the amount of certain proteins in tissue samples, while the MPT test uses a formula to compare the levels of several genes. Both tests utilize samples already collected for diagnosis, minimizing additional risk to participants.

These tests focus on understanding gene patterns rather than introducing new drugs or treatments into the body, making them low risk compared to other medical trials. Prospective participants should inquire about any potential risks or discomforts associated with the sample collection process. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the CLDN15/VIM and MPT tests because they represent a new approach to diagnosing mesothelioma through biomarker validation. Unlike traditional methods that may rely on imaging and invasive procedures, these tests focus on detecting specific biomarkers in pleural biopsy samples, potentially allowing for earlier and more accurate diagnosis. This could lead to better-targeted treatments and improved outcomes for patients by identifying the disease at a stage when interventions may be more effective.

What evidence suggests that this method is effective for determining stage and prognosis of mesothelioma?

Research has shown that the CLDN15/VIM test, which participants in this trial may undergo, holds promise for diagnosing malignant pleural mesothelioma, a type of cancer. Claudin-15, a component of this test, appeared in 83% of mesothelioma samples, suggesting it could be a strong marker for identifying the disease. Studies also suggest that certain gene patterns related to Claudin-15 link to longer survival.

The MPT test, another diagnostic tool evaluated in this trial, helps predict patient outcomes over time. One analysis associated it with better survival outcomes. Both tests aim to provide better insights into the stage and likely progress of mesothelioma, guiding treatment decisions. ^{1 2 3 6 7}

Who Is on the Research Team?

Raphael Bueno

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with malignant pleural mesothelioma who are undergoing various procedures like VATS resections, diagnostic pleural biopsy, or pleuroscopy. It's not suitable for patients deemed unfit for surgery, treatment, or diagnosis.

Inclusion Criteria

I have been diagnosed with malignant pleural mesothelioma and am undergoing pleuroscopy.

I am an adult diagnosed with mesothelioma and will have a biopsy.

I have been diagnosed with mesothelioma and am undergoing a specific type of surgery.

Exclusion Criteria

I have been deemed unsuitable for surgery.

Any patient who is found to be unsuitable for treatment

Any patient who is found to be unsuitable for diagnosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Specimen Collection

Obtaining pleural specimens at the time of routine diagnostic biopsy during the participant's standard treatment

During standard treatment

Analysis

Studying the tissue to determine if the new method of staging and prognosis is accurate and valid

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CLDN15/VIM Test
• MPT Test

Trial Overview The study is evaluating new tests called MPT Test and CLDN15/VIM Test to better determine the stage and prognosis of malignant pleural mesothelioma in individuals undergoing specific medical procedures.

How Is the Trial Designed?

Group I: MRiS Experimental Treatment 2 Interventions

* The specimens to be collected will include at least five pleural biopsy samples * MPT test and the CLDN15/VIM test will be performed

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 58 patients with malignant pleural mesothelioma (MPM), serum levels of soluble mesothelin-related protein (SMRP) and fibulin-3 were found to correlate with initial tumor volume, indicating their potential as diagnostic biomarkers.

However, while SMRP and fibulin-3 levels correlated with tumor size at baseline, they were not effective in tracking tumor response to treatment over time in the immunotherapy trial, suggesting limitations in their prognostic utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial. Katz, SI., Roshkovan, L., Berger, I., et al.[2022]

The study developed novel prognostic models for malignant pleural mesothelioma using tumor characteristics (like tumor volume), molecular signatures (claudin-15-to-vimentin ratio), and patient factors, achieving higher predictive accuracy than existing models.

In patients undergoing pleurectomy and decortication, a poor risk MPT combined with a tumor volume greater than 200 cm³ significantly increased the risk of poor outcomes, highlighting the importance of these factors in treatment planning and clinical trial stratification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelioma Risk Score: A New Prognostic Pretreatment, Clinical-Molecular Algorithm for Malignant Pleural Mesothelioma. Yeap, BY., De Rienzo, A., Gill, RR., et al.[2022]

Soluble mesothelin-related proteins (SMRP) are an FDA-approved biomarker for malignant pleural mesothelioma (MPM), providing diagnostic, monitoring, and prognostic value, making them crucial for early detection in high-risk populations.

Osteopontin shows promise as a prognostic biomarker for MPM, although its diagnostic utility is lower, while other potential biomarkers like calretinin and fibulin 3 require further validation in large-scale studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network. Pass, HI., Alimi, M., Carbone, M., et al.[2021]

The MESOMARK assay for measuring soluble mesothelin-related peptides (SMRP) is a reliable and robust tool, showing high precision and stability, making it suitable for clinical use in detecting malignant pleural mesothelioma (MPM).

In a study of 500 cancer patients, including 88 with MPM, the assay revealed significantly elevated SMRP levels in MPM patients (7.5 nmol/L) compared to healthy individuals (1.5 nmol/L), indicating its potential as a biomarker for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MESOMARK: a potential test for malignant pleural mesothelioma. Beyer, HL., Geschwindt, RD., Glover, CL., et al.[2022]

Claudin-15 (CLDN15) was identified as a novel positive marker for malignant pleural mesotheliomas (MPMs), with 83% of MPM tissue samples testing positive, making it more effective than other markers like calretinin and WT-1.

The specificity of CLDN15 for MPMs was high at 92%, with rare detection in non-mesothelial tumors, suggesting it could improve diagnostic accuracy for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma. Watanabe, M., Higashi, T., Ozeki, K., et al.[2021]

The novel 2-hit panel using Claudin-4 and BAP1 effectively differentiates between malignant mesothelioma and metastatic carcinoma, showing 100% specificity for Claudin-4 in identifying metastatic carcinomas and 88% negativity for BAP1 in mesotheliomas.

This study analyzed 49 malignant mesotheliomas and 49 metastatic carcinomas, demonstrating that the panel can accurately classify these conditions in cytology and biopsy specimens, making it a valuable diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas. Bernardi, L., Bizzarro, T., Pironi, F., et al.[2021]

Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis, primarily due to its resistance to current therapies and the lack of effective early diagnostic biomarkers.

The review highlights several promising biomarkers for early detection of MM, such as mesothelin and microRNAs, which could lead to improved patient monitoring and tailored therapies, ultimately enhancing survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update. Chen, Z., Gaudino, G., Pass, HI., et al.[2022]

Immunohistochemistry using specific antibody panels is crucial for accurately diagnosing malignant mesothelioma (MM), particularly distinguishing it from other neoplasms like adenocarcinoma, with good sensitivity and specificity for the epithelial variant.

However, the accuracy of these antibody panels is lower for diagnosing sarcomatous MM and differentiating it from squamous cell carcinoma and other carcinomas, highlighting the need for evidence-based guidelines on the optimal selection of markers for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Marchevsky, AM.[2021]

A study involving 2,769 patients with benign asbestos-related diseases identified calretinin and mesothelin as potential biomarkers for early detection of malignant mesothelioma (MM), achieving a combined sensitivity of 46% at a specificity of 98%.

This research is significant as it is the first prospective cohort study to evaluate these biomarkers in prediagnostic plasma samples, suggesting that using a combination of markers could enhance early detection of MM, although the impact on mortality remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers. Johnen, G., Burek, K., Raiko, I., et al.[2021]

Malignant pleural mesothelioma (MPM) currently lacks accurate biomarkers for diagnosis and treatment prediction, making it challenging to manage, but several promising candidates are emerging, including mesothelin and circulating proteomic signatures.

While the current diagnostic standard involves a combination of immunohistochemical markers, there is a need for more sensitive and specific non-invasive markers, which require further validation before they can be used in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The established and future biomarkers of malignant pleural mesothelioma. Panou, V., Vyberg, M., Weinreich, UM., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8557128/

Mesothelioma Risk Score: A New Prognostic Pretreatment ... Notably, cluster E was associated with significantly longer survival compared to clusters B-E, B-S and S, and the expression ratio of Claudin-15 (CLDN15) and ...

2. withpower.com withpower.com/trial/phase-mesothelioma-9-2018-b3caf

Biomarker Validation Tests for Mesothelioma Research shows that Claudin-15 is a reliable marker for diagnosing malignant pleural mesothelioma, with 83% of mesothelioma samples testing positive for it, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10353315/

Malignant mesothelioma tumours: molecular pathogenesis ... This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.

4. oaepublish.com oaepublish.com/articles/2394-4722.2023.17

Diagnostic, prognostic, and therapeutic implications of ... This review summarizes the progress in diagnosis, prognosis, and therapeutics derived by genomics and tumor profiling of PM tumors.

5. paperdigest.org paperdigest.org/grant/?grant_id=nih_9750047

Prospective Validation of Prognostic and Predictive Molecular ... ABSTRACT · Malignant pleural mesothelioma (MPM), a devastating asbestos-induced cancer, has <10% 5-yr survival. Treatments are few and limited.

6. researchgate.net researchgate.net/figure/CLDN-15-is-under-expressed-in-MPM-patients-with-history-of-asbestos-exposure-The-number_fig3_315476655

CLDN-15 is under-expressed in MPM patients with history ... CLDN-15 is under-expressed in MPM patients with history of asbestos exposure. The number of patients per group is demonstrated in the figure.

7. stacks.cdc.gov stacks.cdc.gov/view/cdc/210614

Validation of a Gene Expression Test for Mesothelioma ... A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test ...