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Lung Cancer Prevention Screening Programme in Italy (RISP)

Primary Purpose

Lung Cancer, COPD (Chronic Obstructive Pulmonary Disease) With Acute Lower Respiratory Infection, Cardiovascular Diseases

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
early lung cancer detection
blood test
Sponsored by
Ugo Pastorino
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Lung Cancer focused on measuring lung cancer, LDCT, cytisine, screening, smoking cessation, DOPC, cardiovascular diseases, primary prevention, secondary prevention, RCT, microRNA, biomarkers

Eligibility Criteria

55 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Active smoker (≥ 30 packs/year) Former heavy smoker for ≤ 15 years (≥ 30 packs/year) Absence of tumors for at least 5 years Signature of informed consent for studio enrollment and processing of personal data Exclusion Criteria: Severe chronic disease (e.g. severe respiratory and/or renal and/or hepatic and/or cardiac failure) Severe psychiatric problems Abuse of alcohol or other substances (including previous)

Sites / Locations

  • Chiara BovolentaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Standard arm

Risk-based arm

Arm Description

Volunteers with a negative baseline LDCT will repeat LDCT after the first screening with an annual interval (according to guidelines)

Volunteers with a negative baseline LDCT will repeat LDCT after the first screening with an interval of two years.

Outcomes

Primary Outcome Measures

Change in lung cancer incidence
Change in lung cancer incidence: evaluate the impact on lung cancer incidence through LDCT at annual or biennial intervals.
Change in lung cancer specific and overall mortality
Change in lung cancer specific and overall mortality: evaluate the impact on lung cancer mortality through LDCT at annual or biennial intervals.
Change in smoking status
Change in the percentage of smokers
Molecular risk profile through assessing the value of microRNA in blood and tissue samples
MicroRNA expression profile, using TaqMan microfluidic cards: increased efficiency of lung cancer diagnosis by requiring less CT examinations while retaining the ability to diagnose lung cancer at curative state.

Secondary Outcome Measures

Full Information

First Posted
March 1, 2023
Last Updated
March 13, 2023
Sponsor
Ugo Pastorino
Collaborators
Presidio Ospedaliero Santo Spirito, Pescara, IRCCS Centro di Riferimento Oncologico di Basilicata, Potenza, Azienda Ospedaliera Pugliese Ciaccio, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Azienda Ospedaliera dei Colli, Azienda Ospedaliero-Universitaria di Parma, IRCCS in Tecnologie Avanzate e Modelli Assistenziali in Oncologia di Reggio Emilia, Reggio Emilia, Istituto Nazionale dei Tumori Regina Elena, Roma, Ospedale Policlinico San Martino, A.O. Ospedale Papa Giovanni XXIII, Azienda Ospedaliero, Universitaria Ospedali Riuniti, Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento, San Luigi Gonzaga Hospital, Istituto Tumori Giovanni Paolo II, BARI, Azienda Ospedaliera per l'Emergenza Canizzaro, Azienda Ospedaliero-Universitaria Careggi, Istituto Oncologico Veneto IRCCS
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1. Study Identification

Unique Protocol Identification Number
NCT05766046
Brief Title
Lung Cancer Prevention Screening Programme in Italy
Acronym
RISP
Official Title
Early Diagnosis of Lung Cancer of the Italian Pulmonary Screening Network (RISP): Comparative Analysis for the Use of Low Dose Computed Tomography and Promotion of Primary Prevention Interventions in Subjects at High Risk for Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 17, 2022 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ugo Pastorino
Collaborators
Presidio Ospedaliero Santo Spirito, Pescara, IRCCS Centro di Riferimento Oncologico di Basilicata, Potenza, Azienda Ospedaliera Pugliese Ciaccio, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Azienda Ospedaliera dei Colli, Azienda Ospedaliero-Universitaria di Parma, IRCCS in Tecnologie Avanzate e Modelli Assistenziali in Oncologia di Reggio Emilia, Reggio Emilia, Istituto Nazionale dei Tumori Regina Elena, Roma, Ospedale Policlinico San Martino, A.O. Ospedale Papa Giovanni XXIII, Azienda Ospedaliero, Universitaria Ospedali Riuniti, Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento, San Luigi Gonzaga Hospital, Istituto Tumori Giovanni Paolo II, BARI, Azienda Ospedaliera per l'Emergenza Canizzaro, Azienda Ospedaliero-Universitaria Careggi, Istituto Oncologico Veneto IRCCS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This prospective randomized multicentered clinical study aims at implementing early diagnosis of lung cancer in high-risk heavy smokers in the Italian population. The main goal of the study is to develop a nationwide lung cancer prevention screening with high quality standard, similar to that of other screening programs i.e. breast, colon and cervix ongoing in Italy. The Italian Pulmonary Screening Network (RISP) includes 18 centers, which will promote primary prevention by offering a smoking cessation program (i.e. counselling and anti-smoking cytisine-based therapy) and secondary prevention by screening volunteers with chest Low Dose Computed Tomography (LDCT). The primary objective of the study is to demonstrate the non-inferiority of a risk-based screening strategy (less intensive, every 2 years) compared to the standard annual screening, in terms of stage I/II lung cancer incidence. Furthermore, the study aims to provide evidence whether blood biomarkers screening intervals can improve the efficiency of lung cancer screening by requiring less CT examinations while retaining the ability to diagnose lung cancer at curative state.
Detailed Description
Tobacco smoking is the most relevant cause of avoidable death in all high-income countries, including the European Union and Italy. Smoking increases the risk of dying from emphysema by 10 times, doubles that of having a stroke, and increases two to four times that of being affected by a heart attack. In addition, the carcinogenic substances contained in tobacco smoke are responsible for about 90% of lung cancers, but also for most cancers of the oral cavity, larynx and bladder. Therefore, the main causes of death attributable to tobacco smoke are cancers, cardiovascular and respiratory diseases. Lung cancer is a serious and far-reaching health problem with reduced survival after 5 years. Seventy per cent of lung cancers are at an advanced clinical stage and difficult to treat when the first symptoms occur, and a certain diagnosis is made. Lung cancer mainly affects people over the age of 50, with a peak incidence around 70-75 years. Over a third of deaths attributed to smoking are between 35 and 69 years of age. For long time it was not possible to have a certain diagnosis by diagnostic tests. Only at the end of the '90s, it became clear that computed tomography allows lung cancer to be detected at an early stage (stage I), before symptoms occur. Large-scale randomized clinical trials (RCTs) have shown that early detection of lung cancer by CT can reduce lung cancer mortality between 20% and 39%, according to the duration of the intervention. In particular, LDCT screening has been shown to significantly reduce lung cancer mortality by 8-26% for men and 26-61% in women. International lung cancer screening guidelines, currently adopted in the United States, recommend repeating LDCT at annual intervals. However, annual chest LDCT screening has heavy economic impact and can induce radiation-related damage. Recent studies have shown that the first LDCT screening exam provides information on individual risk thus allowing the personalization of the screening interval. In particular, there are indications that screening interval can be extended safely for low-risk individuals. For example, several studies show that individuals with a negative baseline exam have a substantially lower risk than those with a positive baseline exam. A randomized prospective assessment of risk-based screening intervals therefore has the potential to improve efficiency and reduce the economic-health impact of lung cancer screening. In fact, a personalized screening protocol has a less serious economic impact, both at the instrumental level and in terms of the commitment of the radiological staff. In this context, the RISP network aims to promote a nationwide early diagnosis program with LDCT that reduces mortality from lung cancer, and at the same time, brings benefit in primary prevention of smoking-related diseases, such as chronic obstructive pulmonary diseases (COPD) and other cardiovascular diseases. RISP will start lung screening in a gradual and controlled way, through a network of reference centers with multidisciplinary clinical competence that provide adequate coverage of the territory, and meanwhile a level of quality fitting to the standards currently achieved in the screening of other cancers (breast, cervix, colon). A systematic screening program will also increase the percentage of lung cancer patients eligible for early-stage surgical resection from the current 25% (without screening) to 50-60%. At baseline- each volunteer will undergo: a baseline questionnaire (e.g. socio-demographic, smoking habits, etc) with anti-smoking counseling program that includes cytisine-based anti-smoking therapy. blood sampling for the assessment of the inflammatory and metabolic profile (i.e. bio-markers) (optional) evaluation of respiratory function and measurement of carbon monoxide (CO) chest LDCT without contrast anthropometric evaluation (e.g. weight, height, BMI, etc) Follow-up- each randomized volunteer will undergo: clinical examinations of LDCT blood sampling and CO after 12 months of follow-up or 24 months depending on the arm to which they belong. Imaging will be performed by volumetric acquisition with a computed tomography scanner equipped with advanced technology hardware and software, including an AI-based second reading that will be validated by a radiologists panel. All data will be entered into a password-protected database. The protection of the identity of the subjects will be guaranteed by assigning unique participation numbers specific to the study. In a separate database, accessible only by the principal investigator or assigned team members, the unique identification number can be linked to participants' names and addresses for the purposes of local and central administrative processes such as scheduling scans, sending invitation letters, sending screening results and questionnaires for topics, and collecting follow-up information. All volunteer samples and paper/electronic files will be destroyed 15 years after completion of the study. Participants are assured that no personal data will be published in articles, reports or other study documentation. Randomization will be carried out using real-time automated statistical software: eligible subjects will be randomly assigned to one of the two intervention arms (A, B) with a 1:1 ratio.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, COPD (Chronic Obstructive Pulmonary Disease) With Acute Lower Respiratory Infection, Cardiovascular Diseases
Keywords
lung cancer, LDCT, cytisine, screening, smoking cessation, DOPC, cardiovascular diseases, primary prevention, secondary prevention, RCT, microRNA, biomarkers

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7324 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard arm
Arm Type
Experimental
Arm Description
Volunteers with a negative baseline LDCT will repeat LDCT after the first screening with an annual interval (according to guidelines)
Arm Title
Risk-based arm
Arm Type
Experimental
Arm Description
Volunteers with a negative baseline LDCT will repeat LDCT after the first screening with an interval of two years.
Intervention Type
Diagnostic Test
Intervention Name(s)
early lung cancer detection
Intervention Description
standard treatment for early lung cancer detection with LDCT at one or two years interval
Intervention Type
Other
Intervention Name(s)
blood test
Intervention Description
blood analysis for microRNA and other biomarkers detection
Primary Outcome Measure Information:
Title
Change in lung cancer incidence
Description
Change in lung cancer incidence: evaluate the impact on lung cancer incidence through LDCT at annual or biennial intervals.
Time Frame
3 years
Title
Change in lung cancer specific and overall mortality
Description
Change in lung cancer specific and overall mortality: evaluate the impact on lung cancer mortality through LDCT at annual or biennial intervals.
Time Frame
5 years
Title
Change in smoking status
Description
Change in the percentage of smokers
Time Frame
3 years
Title
Molecular risk profile through assessing the value of microRNA in blood and tissue samples
Description
MicroRNA expression profile, using TaqMan microfluidic cards: increased efficiency of lung cancer diagnosis by requiring less CT examinations while retaining the ability to diagnose lung cancer at curative state.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Active smoker (≥ 30 packs/year) Former heavy smoker for ≤ 15 years (≥ 30 packs/year) Absence of tumors for at least 5 years Signature of informed consent for studio enrollment and processing of personal data Exclusion Criteria: Severe chronic disease (e.g. severe respiratory and/or renal and/or hepatic and/or cardiac failure) Severe psychiatric problems Abuse of alcohol or other substances (including previous)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chiara Bovolenta, PhD
Phone
0223903928
Email
chiara.bovolenta@istitutotumori.mi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ugo Pastorino, MD
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chiara Bovolenta
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chiara Bovolenta, PhD
Phone
0223903928
Email
chiara.bovolenta@istitutotumori.mi.it
First Name & Middle Initial & Last Name & Degree
Ugo Pastorino, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35908731
Citation
Pastorino U, Ladisa V, Trussardo S, Sabia F, Rolli L, Valsecchi C, Ledda RE, Milanese G, Suatoni P, Boeri M, Sozzi G, Marchiano A, Munarini E, Boffi R, Gallus S, Apolone G. Cytisine Therapy Improved Smoking Cessation in the Randomized Screening and Multiple Intervention on Lung Epidemics Lung Cancer Screening Trial. J Thorac Oncol. 2022 Nov;17(11):1276-1286. doi: 10.1016/j.jtho.2022.07.007. Epub 2022 Jul 28.
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Citation
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Citation
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Citation
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32997182
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Links:
URL
https://cordis.europa.eu/project/id/848294
Description
4-IN THE LUNG RUN: towards INdividually tailored INvitations, screening INtervals, and INtegrated co-morbidity reducing strategies in lung cancer screening
URL
https://www.ncbi.nlm.nih.gov/books/NBK568586/pdf/Bookshelf_NBK568586.pdf
Description
Cancer Intervention and Surveillance Modeling Network (CISNET) Lung Cancer Working Group.

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Lung Cancer Prevention Screening Programme in Italy

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