Clinical trial NCT02500693: Circulating Tumor Cells in Lung Cancer Screening
Official title: Circulating Tumor Cells and Early Diagnosis of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Neoplasms
Pulmonary Disease, Chronic Obstructive
Keywords: Lung Cancer, Screening, COPD
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2015-07-16
Enrollment: 683
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This trial is intended to evaluate the value of circulating tumor cells (CTC), in combination with unenhanced (without injection of contrast media) low dose (to limit the effective radiation dose below 1,5 mSv) chest computed tomography (LDCT) in the screening of Lung cancer (LC).

LDCT screening was shown to reduce LC mortality in smokers and ex-smokers, older than 55 years, with a history of more than 30 pack-years. LDCT however shows a close to 30% rate of false positive that require repeat follow-up and also invasive investigations, but also false negatives with metastatic LC being discovered between screening rounds.

Migration of circulating tumor cells (CTC) is an early event of carcinogenesis and characterizes aggressive cancers. We recently showed that CTC can be detected with the ISET technique in a population at high risk for LC, i.e. COPD patients before LC was detectable on LDCT.

The study will focus on patients at very high risk for lung cancer i.e. smokers and ex-smokers suffering Chronic Obstructive Pulmonary Disease (COPD).

The study will enroll 600 participants who will undergo three rounds of screening at one year intervals, each round combining search for CTC on a blood sample and LDCT. Each participant will be followed for at least one year after the last screening round


Eligibility criteria: Inclusion Criteria:

* Age 55 years or more
* 30 or more pack-years of cigarette smoking history
* Former smokers: quit smoking within the previous 15 years
* Signed informed consent form
* Presence of COPD
* Affiliation to the French social security system

Exclusion Criteria:

* Chest CT examination in the 12 months prior to eligibility assessment(1)
* Treatment for, or evidence of, any cancer other than skin basocellular carcinoma in the 5 years prior to eligibility assessment
* Pneumonia or acute respiratory infection treated with antibiotics in the 12 weeks prior to eligibility assessment
* Unexplained weight loss of more than 15 10%pounds in the 12 months prior to eligibility assessment
* Recent hemoptysis
* History of lung volume reduction with coils, glue or valves°
* Metallic implants or devices in the chest or back, such as pacemakers or Harrington fixation rods
* Participation in another cancer screening trial
* Participation in a cancer prevention study, other than a smoking cessation study
* Vulnerable persons: adults under guardianship, adults under trusteeship or persons deprived of their liberty, patients under 18 years old
* Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk

  1. Many COPD patients will have had a previous chest CT examination. This has become common in medical practice, especially in patients with chronic lung diseases such as COPD patients. Including such patients would introduce huge bias in the study by artificially focusing on rapidly growing cancers. Redoing a CT in a screening intend in a patient who recently underwent this investigation would also unnecessarily enhance irradiation in these patients. It should be note that in the NLST trial "previous chest CT (≤ 18 months)" was a key exclusion criterion \[NLST Radiology 2011\].

Primary outcomes:
measure: Rate of detection of circulating tumor cells in patients who will have a LC detected during the study
timeFrame: 3 years
Secondary outcomes:
measure: Rate of detection of CTC in the whole study population
timeFrame: once a year for 3 years
measure: Circulating tumor cells
timeFrame: once a year for 3 years
measure: Time span between detection of CTC and detection of lung cancer with LDCT and vice versa
timeFrame: once a year for 3 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Hôpital Nord
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital TENON
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU de Rennes
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: CHU de Rouen
city: Saint Etienne
country: France
facility: CHU de Saint Etienne
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Charles-Hugo MARQUETTE, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ilie M, Hofman V, Long-Mira E, Selva E, Vignaud JM, Padovani B, Mouroux J, Marquette CH, Hofman P. "Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One. 2014 Oct 31;9(10):e111597. doi: 10.1371/journal.pone.0111597. eCollection 2014.
citation: Marquette CH, Boutros J, Benzaquen J, Ferreira M, Pastre J, Pison C, Padovani B, Bettayeb F, Fallet V, Guibert N, Basille D, Ilie M, Hofman V, Hofman P; AIR project Study Group. Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study. Lancet Respir Med. 2020 Jul;8(7):709-716. doi: 10.1016/S2213-2600(20)30081-3.
citation: Leroy S, Benzaquen J, Mazzetta A, Marchand-Adam S, Padovani B, Israel-Biet D, Pison C, Chanez P, Cadranel J, Mazieres J, Jounieaux V, Cohen C, Hofman V, Ilie M, Hofman P, Marquette CH; AIR Project Study Group. Circulating tumour cells as a potential screening tool for lung cancer (the AIR study): protocol of a prospective multicentre cohort study in France. BMJ Open. 2017 Dec 26;7(12):e018884. doi: 10.1136/bmjopen-2017-018884.