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

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ClinicalTrials.gov Identifier: NCT02247453
Recruitment Status : Active, not recruiting
First Posted : September 25, 2014
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
Ugo Pastorino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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.


Condition or disease Intervention/treatment Phase
Lung Cancer Other: screening Not Applicable

Detailed Description:

Three decades of research have shown that radiological screening of heavy smokers can detect resectable early lung cancers with higher frequency but benefit on mortality is still debated. The preliminary results of the first two randomized spiral-CT screening trials appear conflicting, with one study showing no benefit and the other a limited mortality reduction (-7%). In the next 3-4 years the ongoing randomised trials in Europe will provide conclusive data on the efficacy of CT-screening for lung cancer. Nonetheless, no major impact on mortality is to be expected.

A possible explanation of these finding is that not all aggressive lung tumors arise from identifiable slow-growing precursors, thus suggesting a possible paradigm shift in our understanding of the natural history of lung cancer. In this respect the identification of biologic and molecular features of indolent and aggressive disease could be useful to define clinical predictors of high risk lesions and select suitable cohorts of patients who might benefit of current treatments as well as to identify genetic signatures that might represent novel therapeutic targets.

The investigators recently reported that microRNA (miRNA) expression expression profiles in tumors and, for the first time, also in normal lung tissue are indicative of aggressive lung cancer development and, of remarkable interest, that specific miRNA signatures can be identified in plasma samples of patients up to two years before spiral-CT detection of the disease, and able to identify the occurrence of early metastatic but spiral-CT invisible lung tumors or small spiral-CT detected lesions with aggressive potential.

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.

Overall, the results of this large prospective study will permit to establish the potential of our plasma microRNA assay as a first-line screening test for lung cancer detection in a routine clinical practice for high-risk population screening with a low cost, non toxic and non invasive procedure. Moreover, the related functional studies foreseen in the project could lead to the identification of novel, miRNA targeted, therapeutic approaches for this malignancy.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4119 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Plasma microRNA Profiling as First Line Screening Test for Lung Cancer Detection: a Prospective Study
Study Start Date : January 2013
Actual Primary Completion Date : November 2019
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Screening
Healthy heavy smokers aged 50-75 years
Other: screening

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.





Primary Outcome Measures :
  1. Reduction of false positive cases in lung cancer detection in heavy smokers volunteers through plasma miRNA profiling as a first line screening test [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. overall survival [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247453


Locations
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Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
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Principal Investigator: Ugo Pastorino, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Additional Information:
Publications:

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Responsible Party: Ugo Pastorino, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT02247453     History of Changes
Other Study ID Numbers: INT11-21
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: November 25, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Ugo Pastorino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
lung cancer
clinical trial
screening
microRNA
biomarkers
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases