Overview

This trial is active, not recruiting.

Condition lung cancer
Treatment screening
Phase phase 3
Sponsor Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Start date January 2013
End date January 2018
Trial size 4119 participants
Trial identifier NCT02247453, INT11-21

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose screening
Arm
(Experimental)
Healthy heavy smokers aged 50-75 years
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 Outcomes

Measure
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: 5 years

Secondary Outcomes

Measure
overall survival
time frame: 5 years

Eligibility Criteria

Male or female participants from 50 years up to 75 years old.

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

Additional Information

Official title Plasma microRNA Profiling as First Line Screening Test for Lung Cancer Detection: a Prospective Study
Principal investigator Ugo Pastorino, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.