Clinical trial NCT03562052: Lung Cancer Screening in a Population Exposed to Occupational Lung Carcinogens
Official title: LUng Cancer Screening With Low-dose Computed Tomography in a Population Exposed to Occupational Lung Carcinogens
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer
Keywords: Cancer
Lung
Occupational carcinogens
Tobacco smoking
Screening
Chest CT Scan
Asbestos
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
Collaborators: name: University Hospital, Bordeaux
name: Rennes University Hospital
name: Centre Hospitalier Régional et Universitaire de Brest
name: University Hospital, Caen
name: University Hospital, Rouen
name: Direction Centrale du Service de Santé des Armées
First posted: 2018-06-19
Enrollment: 6000
Sex: ALL
Minimum age (years): 55
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects aged from 55 to 74 years, current smokers smoking 30 pack-years or more or ex-smokers smoking 30 pack-years or more and who have quit smoking for less than 15 years and currently or previously occupationally exposed to lung carcinogens. These subjects are known to be high-risk population for lung cancer.

Brief summary: The good clinical practice guidelines for the surveillance of workers after occupational exposure to lung carcinogens were approved by the Haute Autorité de la Santé (French National Authority for Health) and the Institut National du Cancer (French National Cancer Institute) in December 2015 and one recommendation of these guidelines concerns the setting-up of a trial of low-dose chest computed tomography (CT) lung cancer screening in subjects occupationally exposed to lung carcinogens at high-risk of lung cancer (Expert consensus).

In LUCSO study, the investigators propose to conduct, under strictly defined conditions, a feasibility study of lung cancer screening in a population defined as being at high risk of lung cancer according to these good clinical practice guidelines. This population consists of smokers, aged from 55 to 74 years, currently or previously exposed to International Agency for Research on Cancer lung group 1 lung carcinogens.

The primary objective of this study is to evaluate the complex organization of lung cancer screening in the target population. This evaluation will focus on the following indicators:

* Screening activity indicator: screening coverage rate over two years
* Test quality indicator: validity of self-administered questionnaires to target the high-risk population
* Examination quality indicator: lung cancer detection rate, lung cancer detection rates by stage, validity of low-dose chest CT scan
* Follow-up indicator: smoking cessation rate, mortality rate This trial will be conducted in 8 French departments, by six reference centers specialized in occupational health (SRC).

In view of the exploratory nature of this trial, it is proposed to initially test the feasibility and acceptability of lung cancer screening sequentially over the first two years (Phase 1: 2021-2023, 24 months) in only two SRC (Val-de-Marne and Gironde).

The trial will be conducted in several steps:

1. Identification of subjects currently or previously occupationally exposed to lung carcinogens by a screening invitation letter sent by Departmental Cancer Screening Centers to subjects aged from 55 to 74 years.
2. Evaluation of occupational exposure to lung carcinogens
3. Evaluation of the lung cancer risk level and verification of eligibility
4. Screening procedure: Chest CT scans will be performed by centers specialized in chest imaging
5. Lung cancer follow-up when an abnormality suggestive of lung cancer is demonstrated.

Detailed description: The good clinical practice guidelines for the surveillance of workers after occupational exposure to lung carcinogens were approved by the Haute Autorité de la Santé (French National Authority for Health) and the Institut National du Cancer (French National Cancer Institute) in December 2015 and the Recommendation R12 of these guidelines concerns the setting-up of a trial of low-dose chest computed tomography (CT) lung cancer screening in subjects occupationally exposed to lung carcinogens at high-risk of lung cancer (Expert consensus).

In LUCSO study, the investigators propose to conduct, under strictly defined conditions, a feasibility study of lung cancer screening in a population defined as being at high risk of lung cancer according to these good clinical practice guidelines. This population consists of smokers, aged from 55 to 74 years, currently or previously exposed to International Agency for Research on Cancer lung group 1 lung carcinogens.

The primary objective of this study is to evaluate the organization of lung cancer screening in the target population. This evaluation will focus on the following indicators:

* Screening activity indicator: screening coverage rate over two years
* Test quality indicator: validity of self-administered questionnaires to target the high-risk population
* Examination quality indicator: lung cancer detection rate, lung cancer detection rates by stage, validity of low-dose chest CT scan
* Follow-up indicator: smoking cessation rate, mortality rate

The secondary objectives of the study are:

* Describe the population recruited in each step of the protocol
* Develop a tool to identify subjects exposed to pulmonary carcinogens and with high-risk of lung cancer
* Evaluate the impact of the proposed screening programme on smoking cessation at one, two and three years.
* Evaluate the social impact of the screening campaign
* Conduct a cost-effectiveness analysis of the programme

The proposed study will take place in multidisciplinary and specialized reference centers (SRC) in various French districts participating in the programme, to welcome patients participating. It is organized into six workpackages (WP):

* WP1: Methodology - Epidemiology
* WP2: Evaluation of occupational exposure
* WP3: Imaging
* WP4: Lung cancer follow-up strategy
* WP5: Smoking cessation
* WP6: Medico-economic analysis Six specialized reference centers are proposed in four different regions in order to test a potential region effect and to allow the recruitment by each SRC of about 200 to 600 new eligible subjects per year and per department according to the population and the age pyramid of each department
* SRC1: Centre Intercommunal de Créteil for the Val-de-Marne (94), Seine-et-Marne (77), and Essonne (91) departments
* SRC2: Bordeaux University Hospital for the Gironde (33) department
* SRC3: Rennes University Hospital for the Ille-et-Vilaine (35) department
* SRC4: Brest University Hospital for the Finistère (29) department
* SRC5: Caen University Hospital for the Calvados (14) department
* SRC6: Rouen University Hospital for the Seine-Maritime (76) department

Each of these centers is voluntary and possesses the four essential prerequisites: an occupational health clinic - radiology team with specific skills in chest imaging - pulmonology team or network of pulmonologists specialized in lung cancer - smoking cessation team.

In view of the complexity of this organization, it is proposed to initially test the feasibility and acceptability of the screening programme sequentially for the first two years (24 months) in two SRCs (SRC1 and SRC2): "Phase 1: 2021-2023". It is expected to extend the study to the other SRCs after two years: "Phase 2: 2023-2029". Ad hoc adjustments will be decided for the creation of SRCs in the third year on the basis of the data acquired in the two pilot departments, especially on the expected target population participation rate. Mortality will be monitored at least until 2031.

The trial will be conducted in several steps:

1. Identification of subjects currently or previously occupationally exposed to lung carcinogens by a screening invitation letter sent by Departmental Cancer Screening Centers to subjects aged from 55 to 74 years.
2. Evaluation of occupational exposure to lung carcinogens
3. Evaluation of the lung cancer risk level and verification of eligibility
4. Screening procedure: Chest CT scans will be performed by centers specialized in chest imaging
5. Lung cancer follow-up when an abnormality suggestive of lung cancer is demonstrated.

Eligibility criteria: Inclusion Criteria:

Subjects at high risk of lung cancer: current smokers smoking 30 pack-years or more or ex-smokers smoking 30 pack-years or more and who have quit smoking for less than 15 years and currently or previously occupationally exposed to lung carcinogens. With an algorithm for determination of minimal duration of exposure to occupational carcinogens (according to the type and duration of occupational lung carcinogens)

Exclusion Criteria:

* Presence of clinical signs of lung cancer
* Subjects with a history of lung cancer
* Presence of serious short-term life-threatening comorbidities
* Absence of occupational exposure to lung carcinogens according to the predefined criteria
* Subjects already included in another prospective cohort study
* Subjects already assessed by chest CT scan during the previous year
* No tobacco exposure or insufficient tobacco exposure or smoking cessation for more than 15 years.

Primary outcomes:
measure: Rate of detected lung cancer
timeFrame: Year 1
Secondary outcomes:
measure: Rate of detected lung cancer
timeFrame: Year 2
measure: Rate of detected lung cancer
timeFrame: Day 0
measure: Participation rate
timeFrame: Day 0
measure: Rate of detected lung cancer in subjects exposed to occupational carcinogens
timeFrame: Day 0
measure: Rate of detected lung cancer in subjects exposed to occupational carcinogens
timeFrame: Year 1
measure: Rate of detected lung cancer in subjects exposed to occupational carcinogens
timeFrame: Year 2
measure: Stage of detected lung cancers
timeFrame: Day 0
measure: Stage of detected lung cancers
timeFrame: Year 1
measure: Stage of detected lung cancers
timeFrame: Year 2
measure: Smoking cessation rate obtained in smokers in the sreened population
timeFrame: Year 3
measure: Mortality rate in the sreened population
timeFrame: Year 3
measure: Mortality rate in the sreened population
timeFrame: Year 5
measure: Mortality rate in the sreened population
timeFrame: Year 7
measure: Mortality rate in the non-screened population
timeFrame: Year 3
measure: Mortality rate in the non-screened population
timeFrame: Year 5
measure: Lung cancer rate in non-screened subjects but met at the Occupational Disease Consultation Center
timeFrame: Year 3
measure: Mortality rate in the non-screened population
timeFrame: Year 7
measure: Lung cancer rate in non-screened subjects but met at the Occupational Disease Consultation Center
timeFrame: Year 5
measure: Lung cancer rate in non-screened subjects but met at the Occupational Disease Consultation Center
timeFrame: Year 7
measure: Rate of detected lung cancer and stage of detected lung cancer in the non-screened population
timeFrame: Year 3
measure: Rate of detected lung cancer and stage of detected lung cancer in the non-screened population
timeFrame: Year 5
measure: Rate of detected lung cancer and stage of detected lung cancer in the non-screened population
timeFrame: Year 7
measure: Percentage of subjects participating in all screening (over the three years)
timeFrame: Year 3
measure: Percentage of subjects participating in all screening (over the three years)
timeFrame: Year 4
measure: Percentage of the subjects lost during follow-up in the screened population (follow-up at one year, two years, completion of other complementary exams)
timeFrame: Year 1
measure: Percentage of the subjects lost during follow-up in the screened population (follow-up at one year, two years, completion of other complementary exams)
timeFrame: Year 2
measure: Validity of the detailed personalised self-administered questionnaire for the evaluation of occupational exposures
timeFrame: Day 0
measure: Number of cases recognized as occupational disease (for lung cancer or other occupational diseases)
timeFrame: Year 2
measure: Proportion of invasive diagnostic procedures
timeFrame: Day 0
measure: Proportion of invasive diagnostic procedures
timeFrame: Year 1
measure: Proportion of invasive diagnostic procedures
timeFrame: Year 2
measure: Proportion of non-invasive diagnostic procedures
timeFrame: Day 0
measure: Proportion of non-invasive diagnostic procedures
timeFrame: Year 1
measure: Proportion of non-invasive diagnostic procedures
timeFrame: Year 2
measure: Proportion of serious and non-serious adverse events related to screening
timeFrame: Day 0
measure: Proportion of serious and non-serious adverse events related to screening
timeFrame: Year 1
measure: Proportion of serious and non-serious adverse events related to screening
timeFrame: Year 2
measure: Proportion of subjects stopping smoking at each stage of screening
timeFrame: Day 0
measure: Proportion of subjects stopping smoking at each stage of screening
timeFrame: Year 1
measure: Proportion of subjects stopping smoking at each stage of screening
timeFrame: Year 2
measure: The time period between each step of the screening (evaluation of the exposure, addressing in consultation of occupational diseases, inclusion, different exams of the follow-up)
timeFrame: Day 0
measure: The time period between each step of the screening (evaluation of the exposure, addressing in consultation of occupational diseases, inclusion, different exams of the follow-up)
timeFrame: Year 1
measure: The time period between each step of the screening (evaluation of the exposure, addressing in consultation of occupational diseases, inclusion, different exams of the follow-up)
timeFrame: Year 3
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Subject inclusion
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Year 1
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Year 2
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Year 3
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Year 4
measure: Number of additional radiological examinations performed besides the prescribed CT scans of the protocol
timeFrame: Year 5
measure: Number of hospitalizations
timeFrame: Subject inclusion
measure: Number of hospitalizations
timeFrame: Year 1
measure: Number of hospitalizations
timeFrame: Year 2
measure: Number of hospitalizations
timeFrame: Year 3
measure: Number of hospitalizations
timeFrame: Year 4
measure: Number of hospitalizations
timeFrame: Year 5
measure: Number of lung surgery
timeFrame: Subject inclusion
measure: Number of lung surgery
timeFrame: Year 1
measure: Number of lung surgery
timeFrame: Year 2
measure: Number of lung surgery
timeFrame: Year 3
measure: Number of lung surgery
timeFrame: Year 4
measure: Number of lung surgery
timeFrame: Year 5
measure: Number of chemotherapy
timeFrame: Day 0
measure: Number of chemotherapy
timeFrame: Year 1
measure: Number of chemotherapy
timeFrame: Year 2
measure: Number of chemotherapy
timeFrame: Year 3
measure: Number of chemotherapy
timeFrame: Year 4
measure: Number of chemotherapy
timeFrame: Year 5
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux
city: Bordeaux
country: France
facility: Université de Bordeaux
city: Brest
country: France
facility: Centre Hospitalier Universitaire de Brest
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Toulon
country: France
facility: Hôpital d'Instruction des Armées Sainte-Anne
Study officials:
affiliation: Centre Hospitalier Interconnmunal de Créteil
name: Jean-Claude Pairon, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Delva F, Laurent F, Paris C, Belacel M, Brochard P, Bylicki O, Chouaid C, Clin B, Dewitte JD, Le Denmat V, Gehanno JF, Lacourt A, Margery J, Verdun-Esquer C, Mathoulin-Pelissier S, Pairon JC. LUCSO-1-French pilot study of LUng Cancer Screening with low-dose computed tomography in a smokers population exposed to Occupational lung carcinogens: study protocol. BMJ Open. 2019 Mar 23;9(3):e025026. doi: 10.1136/bmjopen-2018-025026.