Circulating Tumor Cells in Lung Cancer Screening

Pulmonary Disease, Chronic Obstructive Clinical Trial

— AIR  

Official title:

Circulating Tumor Cells and Early Diagnosis of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02500693
• Other study ID #: 15-PP-08
• Status: Completed
• Phase: N/A
• Start date: October 30, 2015
• Est. completion date: October 13, 2020

Study information

• Verified date: January 2018
• Source: Centre Hospitalier Universitaire de Nice
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 683
• Est. completion date: October 13, 2020
• Est. primary completion date: October 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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].

Related Conditions & MeSH terms

• Lung Diseases
• Lung Neoplasms
• Neoplastic Cells, Circulating
• Pulmonary Disease, Chronic Obstructive

Intervention

Biological:
• Isolation of circulating tumor cells (CTC) from veinous blood
Thirty ml of peripheral blood will be collected in buffered EDTA, maintained at 4°C, and processed within 1 hour for filtration. After blood filtration, the membrane will be gently washed with PBS, disassembled from the filtration module, and allowed to air-dry. The determination of CTC number present on filters will be carried out by combining four color immunofluorescent (anti-pancytokeratins/anti-vimentin/DAPI/anti-CD45) staining and cytomorphological examination after Diff-quick and Mayer Hemalun staining in three spots per patient sample. Imaging of immunofluorescent and cytological staining will be performed at x20 magnification using the automated Ariol system. CTCs are identified by relocating images of immunofluorescent and cytological staining.

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CHRU de Lille	Lille
France	Hospices Civils de Lyon	Lyon
France	Hôpital Nord	Marseille
France	CHU de Montpellier	Montpellier
France	CHU de Nancy	Nancy
France	Hôpital Bichat	Paris
France	Hôpital Cochin	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital TENON	Paris
France	CHU de Reims	Reims
France	CHU de Rennes	Rennes
France	CH de Roubaix	Roubaix
France	CHU de Rouen	Rouen
France	CHU de Saint Etienne	Saint Etienne
France	CHU de Strasbourg	Strasbourg
France	CHU de Toulouse	Toulouse
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of detection of circulating tumor cells in patients who will have a LC detected during the study		3 years
Secondary	Rate of detection of CTC in the whole study population		once a year for 3 years
Secondary	Circulating tumor cells	Predictive value of CTC detection for the diagnosis of LC in patients identified as having a pulmonary nodule.	once a year for 3 years
Secondary	Time span between detection of CTC and detection of lung cancer with LDCT and vice versa		once a year for 3 years