Clinical trial NCT00512746: Screening for Lung Cancer in Current or Past Smokers With Chronic Obstructive Pulmonary Disease
Official title: A Randomised Controlled Trial of Surveillance for the Early Detection of Lung Cancer in an at Risk Group [Lung-SEARCH Trial]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Cancer
Precancerous Condition
Keywords: small cell lung cancer
non-small cell lung cancer
precancerous condition
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2007-08-08
Enrollment: 1569
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: RATIONALE: Screening tests or exams may help doctors find lung cancer sooner, when it may be easier to treat.

PURPOSE: This randomized clinical trial is studying screening tests or exams to see how well they work compared to usual care in finding early stage lung cancer in current or past smokers with chronic obstructive pulmonary disease.

Detailed description: OBJECTIVES:

Primary

* To show that the proportion of lung cancer diagnosed at stage I or II is significantly greater in the surveillance arm than in the control arm.

Secondary

* Establish whether sputum cytology and/or cytometry can be employed to stratify patients with chronic obstructive pulmonary disease (COPD) according to their risk of developing incidence lung cancer.
* Identify patients with pre-invasive lesions in their airways and examine the risk of developing lung cancer in patients harboring these lesions.
* Provide an opportunity to archive blood samples from patients under surveillance to enable the identification of markers of disease progression.
* Examine the compliance of regular screening among patients in this high-risk group.
* Determine the proportion of patients in which it is not possible to provide a sputum screening result.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to recruiting site, age, gender, smoking history (current vs ex-smoker) and severity of chronic obstructive pulmonary disease (COPD) (mild vs moderate). Patients are randomized to 1 of 2 arms.

* Control arm: Patients are managed according to the usual practice of their hospital or general practice for their COPD treatment. They undergo no particular investigations except those that may arise due to a change in their clinical condition. Those patients who are not diagnosed with lung cancer during the course of the study are offered a chest x-ray after 5 years of follow-up.
* Surveillance arm: Patients undergo surveillance for 5 years. A sputum sample is collected for cytology and cytometry. If the sputum sample is normal the patient is asked to provide a sputum sample annually. If the sputum sample is abnormal the patient undergoes an annual spiral CT scan followed by autofluorescence bronchoscopy. At bronchoscopy, the following samples are taken: bronchial washings, bronchial brushings, and bronchial biopsies. Bronchoscopy is repeated every 4-12 months depending upon the histology results. If an invasive lesion is found, the patient is referred for treatment via the normal hospital systems. Any remaining sputum sample is stored frozen as part of the tissue bank associated with this trial.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Meets 1 of the following criteria:

  * Current smoker, defined as ≥ a 20 pack year smoking history and/or 20 year duration of smoking
  * Ex-smoker who has quit smoking within the past 8 years AND has ≥ a 20 pack year smoking history and/or 20 year duration of smoking
* Mild to moderate chronic obstructive pulmonary disease (COPD) as defined by the GOLD criteria

  * Mild COPD: FEV_1/forced vital capacity (FVC) \< 70%; FEV_1 ≥ 80% of predicted\*
  * Moderate COPD: FEV_1/FVC \< 70%; FEV_1 50-80% of predicted\* NOTE: \*Spirometric values will be obtained post bronchodilator according to the recommendations in the GOLD criteria

Exclusion criteria:

* Inadequate lung function (FEV_1 \< 50% of predicted after bronchodilator)

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Life expectancy must be at least 5 years

Exclusion criteria:

* History of malignant disease within the past 5 years except non-melanomatous skin cancers
* Other serious co-morbidity
* Evidence of severe or uncontrolled systemic diseases that, in the view of the investigator, makes it undesirable for the patient to participate in this trial
* Any disorder making reliable informed consent impossible
* Unlikely to co-operate with a 5 year follow-up

PRIOR CONCURRENT THERAPY:

* Patients may receive all concurrent therapy deemed to provide adequate care as decided by their medical doctors

Primary outcomes:
measure: Proportion of lung cancer that is diagnosed as stage I or II
timeFrame: 5 years
Secondary outcomes:
measure: Uptake of screening (the proportion of patients in the surveillance arm who undergo annual screening, among those invited to attend)
timeFrame: 5 Years
measure: Proportion of patients in the surveillance arm who have abnormal sputum cytology
timeFrame: 5 Years
measure: Proportion of patients in the surveillance arm who have abnormal sputum cytometry
timeFrame: 5 Years
measure: Death from lung cancer
timeFrame: Up to 15 years
measure: Proportion of failed sputum samples (i.e., where it is not possible to obtain adequate sputum samples)
timeFrame: 5 Years
measure: Prevalence of pre-invasive disease in patients in the surveillance arm with abnormal cytometry
timeFrame: 5 Years
measure: Number of patients in the surveillance arm with pre-invasive lesions who develop lung cancer locally and at remote sites within the lung
timeFrame: 5 Years
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: England
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
state: England
city: London
country: United Kingdom
facility: Chelsea Westminster Hospital
state: England
city: London
country: United Kingdom
facility: Royal Brompton Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital - London
state: England
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: England
city: Belfast
country: United Kingdom
facility: Respiratory Research Office Belfast City Hospital
state: Northern Ireland
Study officials:
affiliation: University College London Hospitals
name: Stephen G. Spiro
role: STUDY_CHAIR
References:
citation: Spiro SG, Hackshaw A; LungSEARCH Collaborative Group. Research in progress--LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group. Thorax. 2016 Jan;71(1):91-3. doi: 10.1136/thoraxjnl-2015-207433. Epub 2015 Jul 2.