Clinical trial NCT04106973: Mesothelioma Early Detection by VOCs
Official title: Identification of Biomarkers for the Early Detection of Mesothelioma
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pleural Mesothelioma
Asbestos Exposure
Pleural Plaque
Keywords: Pleural Mesothelioma
Bilateral Pleural Plaques
Asbestos Exposure
Exhaled breath analysis
VOCs
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
Collaborators: name: International Association of Heat and Frost Insulators and Allied Workers
name: Owlstone Ltd
name: Fujirebio Diagnostics, Inc.
First posted: 2019-09-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with histologically confirmed pleural mesothelioma, and individuals with an asbestos exposure and radiological evidence of bilateral pleural plaques or pleural thickening without evidence of mesothelioma. The majority of asbestos exposed participants with bilateral pleural thickening or pleural plaques and no mesothelioma will be active or retired members of the International Association of Heat and Frost Insulators and Allied Workers Union.

Brief summary: This is a two phase study, The first phase (phase 1) will identify potential biomarkers among asbestos exposed individuals with pleural mesothelioma. The second phase (phase 2), is a double blinded case-matched controlled study to determine the predictive capability, sensitivity, and specificity of these biomarkers in detecting early stage pleural mesothelioma. Biomarkers in the form of volatile organic compounds (VOC) in exhaled breath samples from subjects with either pleural mesothelioma or pleural plaques, will be evaluated. A biomarker present in serum will also be concurrently evaluated in the same cohort. The soluble serum biomarker mesothelin related peptides (SMRP), which has been posited as a biomarker for mesothelioma, will be analyzed for its relationship to the breath VOC profile.

Detailed description: Mesothelioma is a rare, aggressive and treatment-resistant disease and, in the United States, is caused almost exclusively by exposure to asbestos fibers. There is often a lengthy latency period of 40-50 years between exposure and disease onset. The median age of diagnosis is 65 years while the median survival time after diagnosis of pleural mesothelioma without treatment is 9 months. Symptoms, where present, may be non-specific, which further contributes to delayed diagnosis.

In this study, the volatile organic compound (VOC) profile of exhaled breath from subjects with histologically confirmed mesothelioma will be compared against case-matched control subjects with bilateral pleural plaques or bilateral pleural thickening. Putative markers will then be tested against a blinded cohort to test predictive value of the markers.

This study seeks to identify markers for mesothelioma using a non-invasive technique which samples volatile organic compounds (VOC) in the breath of test subjects (Owlstone Medical Ltd, Cambridge, England).

A comparison of the participant's VOC profile will be made with an FDA-approved, serum-based assay (Lumipulse Mesomark®, Fujirebio Diagnostics Inc., Malvern, PA) of the participant's soluble mesothelin related peptides (SMRP) to discern parameters of efficacy..

Eligibility criteria: Inclusion Criteria

* Male or Female over 18 years of age
* Clinical diagnosis of pleural mesothelioma or presence of pleural plaques on X-Ray
* Documented exposure to asbestos
* Must be able to provide breath sample
* Must be able to provide relevant medical information

Exclusion Criteria

* Presence of malignancies other that mesothelioma within the past 6 months
* Treatment for any malignancies other than mesothelioma within the past 6 months
* Inability to provide past clinical information
* Inability to perform breath collection procedure
* Smoking or consuming alcohol within two hours of conducting breath collection procedure

Primary outcomes:
measure: VOC markers in breath samples. Predictive capability, sensitivity and specificity of biomarkers present in volatile organic compounds (VOC) for the early detection of pleural Mesothelioma in patients exposed to asbestos.
timeFrame: At study completion, approximately 2 years
Secondary outcomes:
measure: Predictive capability, sensitivity and specificity of Soluble Mesothelin Related Peptides (SMRP) in serum when combined with VOC biomarkers for pleural mesothelioma.
timeFrame: At study completion, approximately 2 years
Other outcomes:
Locations:
city: Farmington Hills
country: United States
facility: Consultants in Sleep and Pulmonary Medicine
state: Michigan
Study officials:
affiliation: Ascension Providence Hospital, Southfield
name: Michael R Harbut, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Ascension Providence South East Michigan
name: David M Svinarich, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Gennaro G, Dragonieri S, Longobardi F, Musti M, Stallone G, Trizio L, Tutino M. Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure. Anal Bioanal Chem. 2010 Dec;398(7-8):3043-50. doi: 10.1007/s00216-010-4238-y. Epub 2010 Oct 6.
citation: Oliver LC, Welch LS, Harbut MR. Comparison of B readers' interpretations of chest radiographs for asbestos related changes. Acad Radiol. 2004 Dec;11(12):1397-9; author reply 1402-4. doi: 10.1016/j.acra.2004.09.010. No abstract available.