Biomarker Validation Tests for Mesothelioma

Recruiting in Palo Alto (17 mi)

Overseen by Raphael Bueno

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Unsuitable for surgery, treatment, diagnosis

No Placebo Group

Trial Summary

What is the purpose of this trial?

This research study is evaluating a new method for determining stage and prognosis of individuals with malignant pleural mesothelioma.

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 data supports the effectiveness of the CLDN15/VIM Test, Claudin-15, Vimentin, MPT Test treatment 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, which is comparable to other markers. Additionally, the mesothelioma prognostic test (MPT) uses the claudin-15-to-vimentin expression ratio as a molecular signature associated with survival, suggesting its potential role in prognosis. ^{1 2 3 4 5}

How does this treatment differ from other treatments for mesothelioma?

This treatment focuses on using biomarkers like calretinin and mesothelin for early detection of mesothelioma, which is unique compared to traditional treatments that often start after symptoms appear. By identifying the disease earlier, it may allow for more timely interventions, although its impact on reducing mortality is still being studied. ^{6 7 8 9 10}

Research Team

Raphael Bueno

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• CLDN15/VIM Test (Biomarker Test)
• MPT Test (Biomarker 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.

Participant Groups

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+

Dr. Benjamin L. Ebert

Dana-Farber Cancer Institute

Chief Executive Officer

MD from Harvard Medical School, PhD from Oxford University

Dr. Craig A. Bunnell

Dana-Farber Cancer Institute

Chief Medical Officer since 2012

MD from Harvard Medical School, MPH from Harvard School of Public Health, MBA from MIT Sloan School of Management

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Mesothelioma Risk Score: A New Prognostic Pretreatment, Clinical-Molecular Algorithm for Malignant Pleural Mesothelioma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. Ireland 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. [2022]

6. England 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network. [2021]

8. England pubmed.ncbi.nlm.nih.gov

MESOMARK: a potential test for malignant pleural mesothelioma. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The established and future biomarkers of malignant pleural mesothelioma. [2020]