Plasma microRNA Profiling as First Line Screening Test for Lung Cancer Detection: a Prospective Study

NCT02247453 | Active Not Recruiting DMC

• 1 other identifier: INT11-21
• Study Type: interventional
• Target: 4,119
• Locations: 1 country
• Sites: 1

Brief Summary

In the present project we propose a large prospective study in heavy smokers volunteers based on plasma miRNA profiling to assess its efficacy as a first line screening test for lung cancer detection. The study will be articulated in different phases: i) analysis of 1000 plasma samples of disease-free smokers already collected in our biological repository in the last two years ii) de-novo enrollment of 4000 smoking volunteers, collection of their blood samples and inclusion in a program of active surveillance on the basis of their miRNA risk profile iii) assessment of miRNA expression profile using a custom made microfluidic card containing the 24 miRNA previously identified in the diagnostic signatures iii) bioinformatic analyses of miRNA ratios in the cohort in order to determine which individuals are in presence or will develop lung cancer and in particular the aggressive form of the disease iv) assessment of the best diagnostic and treatment algorithm for subjects with suspicious miRNA profiles v) functional validation of miRNAs as novel therapeutic targets using novel cellular genetically engineered models of transformation and patients' tumorgrafts models.

Conditions

Lung Cancer

Keywords

lung cancer; clinical trial; screening; microRNA; biomarkers

Outcome Measures

Primary Outcomes (1)

• Reduction of false positive cases in lung cancer detection in heavy smokers volunteers through plasma miRNA profiling as a first line screening test

  3 years

Secondary Outcomes (1)

• overall survival

  5 years

Study Arms (1)

Screening

EXPERIMENTAL

Healthy heavy smokers aged 50-75 years

Other: screening

Interventions

screening OTHER

All subjects undergo baseline LDCT examination, spirometry and miRNA profiling. Individuals with negative miRNA profile repeat the plasma assay at 3 years. Individuals with low-risk miRNA profile repeat the plasma assay and LDCT at 2 years, without additional diagnostic examinations if not required by the screening protocol. Individuals with high-risk miRNA profile undergo additional diagnostic examinations consisting in PET in case of concurrent suspicious or positive CT, or WB MRI +- needle aspiration biopsy in case of negative CT.

Screening

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• current heavy smokers of ≥ 30 pack/years, aged 50-75, or former smokers with the same smoking habits having stopped from 10 years or less;
• current or former smokers of \< 30 pack/years, aged ≥ 50, with additional risk factors such as family history of lung cancer, prior diagnosis of chronic obstructive pulmonary disease (COPD) or pneumonia, professional exposure to known carcinogens (i.e. asbestos).

You may not qualify if:

• subjects with neoplasms within previous five years-
• subjects with suspected lung nodules under investigation

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (12)

• Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabro E, Croce CM, Pastorino U, Sozzi G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8. doi: 10.1073/pnas.1100048108. Epub 2011 Feb 7.

  PMID: 21300873 BACKGROUND

• Sozzi G, Pastorino U, Croce CM. MicroRNAs and lung cancer: from markers to targets. Cell Cycle. 2011 Jul 1;10(13):2045-6. doi: 10.4161/cc.10.13.15712. No abstract available.

  PMID: 21623159 BACKGROUND

• Pastorino U, Rossi M, Rosato V, Marchiano A, Sverzellati N, Morosi C, Fabbri A, Galeone C, Negri E, Sozzi G, Pelosi G, La Vecchia C. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012 May;21(3):308-15. doi: 10.1097/CEJ.0b013e328351e1b6.

  PMID: 22465911 BACKGROUND

• Boeri M, Pastorino U, Sozzi G. Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J. 2012 May-Jun;18(3):268-74. doi: 10.1097/PPO.0b013e318258b743.

  PMID: 22647364 BACKGROUND

• Pastorino U. Current status of lung cancer screening. Thorac Surg Clin. 2013 May;23(2):129-40. doi: 10.1016/j.thorsurg.2013.01.018.

  PMID: 23566965 BACKGROUND

• Pastorino U, Sverzellati N. Lung cancer: CT screening for lung cancer--do we have an answer? Nat Rev Clin Oncol. 2013 Dec;10(12):672-3. doi: 10.1038/nrclinonc.2013.198. Epub 2013 Nov 5. No abstract available.

  PMID: 24189470 BACKGROUND

• Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, Roz L, Conte D, Grassi M, Sverzellati N, Marchiano A, Negri E, La Vecchia C, Pastorino U. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative MILD trial study. J Clin Oncol. 2014 Mar 10;32(8):768-73. doi: 10.1200/JCO.2013.50.4357. Epub 2014 Jan 13.

  PMID: 24419137 BACKGROUND

• Fortunato O, Boeri M, Verri C, Conte D, Mensah M, Suatoni P, Pastorino U, Sozzi G. Assessment of circulating microRNAs in plasma of lung cancer patients. Molecules. 2014 Mar 10;19(3):3038-54. doi: 10.3390/molecules19033038.

  PMID: 24619302 BACKGROUND

• Sestini S, Boeri M, Marchiano A, Pelosi G, Galeone C, Verri C, Suatoni P, Sverzellati N, La Vecchia C, Sozzi G, Pastorino U. Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening. Oncotarget. 2015 Oct 20;6(32):32868-77. doi: 10.18632/oncotarget.5210.

  PMID: 26451608 BACKGROUND

• Boeri M, Sestini S, Fortunato O, Verri C, Suatoni P, Pastorino U, Sozzi G. Recent advances of microRNA-based molecular diagnostics to reduce false-positive lung cancer imaging. Expert Rev Mol Diagn. 2015 Jun;15(6):801-13. doi: 10.1586/14737159.2015.1041377. Epub 2015 Apr 30.

  PMID: 25924864 BACKGROUND

• Boeri M, Sabia F, Ledda RE, Balbi M, Suatoni P, Segale M, Zanghi A, Cantarutti A, Rolli L, Valsecchi C, Corrao G, Marchiano A, Pastorino U, Sozzi G. Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial. Lancet Reg Health Eur. 2024 Sep 16;46:101070. doi: 10.1016/j.lanepe.2024.101070. eCollection 2024 Nov.

  PMID: 39319217 DERIVED

• Zyla J, Dziadziuszko R, Marczyk M, Sitkiewicz M, Szczepanowska M, Bottoni E, Veronesi G, Rzyman W, Polanska J, Widlak P. miR-122 and miR-21 are Stable Components of miRNA Signatures of Early Lung Cancer after Validation in Three Independent Cohorts. J Mol Diagn. 2024 Jan;26(1):37-48. doi: 10.1016/j.jmoldx.2023.09.010. Epub 2023 Oct 20.

  PMID: 37865291 DERIVED

Related Links

• clinical trial website

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Mass Screening

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis; Health Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Diagnostic Services; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Public Health Practice

Study Officials

• Ugo Pastorino, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: September 25, 2014
• Study Start: January 1, 2013
• Primary Completion: November 1, 2019
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 7, 2024

Record last verified: 2024-03

Locations

IT (1)