Condition category
Cancer
Date applied
31/01/2019
Date assigned
05/04/2019
Last edited
05/04/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Early-stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable by ‘radical treatment’, such as
major surgery or combination radiotherapy and chemotherapy. However, up to 50% of patients die within 2 years and suffer major side-effects. When a rim of fluid surrounds the lung at diagnosis (called Minimal Pleural Effusion (MiniPE)) recurrence risk is high.
In STRATIFY, we are investigating the use of a test called local anaesthetic thoracoscopy (LAT) to detect the spread of cancer to the lining of the lung (pleura). We hope that this study will show that the addition of LAT to standard investigations for lung cancer with small effusions will help in the detection of spread of the cancer cells (metastases).

Who can participate?
Male and female patients of 16 years and over with a diagnosis for stage I-IIIA NSCLC are potentially eligible, subject to all entry criteria being met.

What does the study involve?
Potentially eligible patients will be invited to participate in the screening part of the STRATIFY trial, during which they will be given an ultrasound of the chest to ensure they are suitable to enter the main study.
Eligible Patients choosing to take part in the trial will be examined by their trial doctor/nurse and a record of vital signs (blood pressure, temperature, pulse rate) medical history, general well-being and medication taken.
Patients will have the local anaesthetic thoracoscopy procedure (LAT). LAT involves insertion of slim telescope into the space between the lung and rib-cage. This allows removal of the small amount of fluid that is there and samples (biopsies) to be taken. These biopsies will identify whether the cancer has spread to the lining outside the lung. LAT is not an operation and does not require a general anaesthetic. It is performed using local anaesthetic to ensure patients are comfortable, and is very safe.
Patients will be requested to provide a sample of pleural fluid during the LAT, which will be stored and used for future research in NSCLC. This is optional.
Before and after the LAT, patients will be given a chest x-ray.
Patients will be requested to provide one blood sample which will be stored and used for future research in NSCLC. This is optional.
All follow up continuing after LAT will be carried out as it would for any other patient receiving standard care. Patients will not be asked to attend further clinics for the purposes of the trial; however as part of the trial, we will follow progress distantly for 6 months by looking at clinical records to help decide if performing LATs to look for cancer in the lining of the lung is of overall benefit to patients.

What are the possible benefits and risks of participating?
The possible benefit of taking part in this trial is that patients will receive treatment based on a more accurate staging (description) of the cancer. If pleural spread is discovered, patients will avoid futile and potentially toxic treatments they may otherwise have been exposed to. The trial may also provide information on the treatment of non-small cell lung cancer which could benefit patients in the future.

As well as possible benefits, the trial investigations can also produce side effects.
LAT is a safe procedure with most complications being very rare. The most common risk is discomfort. We do however give pain killers prior to, during and after the procedure to minimise any pain cause by LAT. Other possible complications are all uncommon.
In addition to the possible risks involved with LAT, patients participating in the trial will need to attend the hospital to have the LAT performed which may involve an overnight stay in hospital. Patients will also have one additional blood test on top of those required pre-LAT which they would not have had if you were not participating in the trial.

Where is the study run from?
The study will be co-ordinated by the Cancer Research UK Clinical Trials Unit, in Glasgow, and the Lead site will be the Queen Elizabeth University Hospital, Glasgow. The study will be open at 5 further UK sites: Salford Royal Hospital, Guy's And St Thomas', Southmead Hospital, John Radcliffe Hospital, Wythenshawe Hospital, and one Australian site: Institute for Respiratory Health, Perth

When is the study starting and how long is it expected to run for?
The study is anticipated to open to recruitment in August 2019, until Feb 2021 (18 months).

What is the anticipated start date and the approximate duration of the trial?
The trial is anticipated to start in August 2019 and will have a 3 year duration.

Who is funding the study?
STRATIFY is funded by a grant from the Chief Scientists Office (CSO), Scotland

Who is the main contact?
Laura Alexander
Project Manager
Laura.alexander@glasgow.ac.uk

Trial website

n/a

Contact information

Type

Scientific

Primary contact

Mrs Laura Alexander

ORCID ID

http://orcid.org/0000-0002-4375-3470

Contact details

Project Manager
Cancer Research UK Clinical Trials Unit
(partner in CaCTUS - Cancer Clinical Trials Unit Scotland)
Level 0
The Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

STRATIFY2018

Study information

Scientific title

Staging by thoracoscopy in potentially radically treatable non-small cell lung cancer associated with minimal pleural effusion

Acronym

STRATIFY

Study hypothesis

Lung Cancer is the commonest cause of cancer-related death in the UK. Despite major advances in staging and potentially curative (or radical) treatments (surgery and radiotherapy (RT)), recurrence rates remain high. In patients with Stage I, II and IIIA Non-Small Cell Lung Cancer (NSCLC) 2-year mortality is currently 15%, 30% and 50%, respectively. A likely reason for this is radiologically occult metastatic disease and novel staging tools are urgently required. Recent studies have highlighted minimal pleural effusion (Mini-PE) as a marker of particularly high recurrence risk, and excess mortality following radical treatment. Current guidelines do not address the staging of Mini-PE. Previous studies infer occult pleural metastases (OPM) in up to 80% of patients with Mini-PE but agree other factors may be responsible in others, including co-morbidities and reactive effusion.

Precise pleural staging would resolve this uncertainty and avoid futile treatment toxicities in patients with OPM, who unfortunately cannot be cured with radical treatment. It may also reduce recurrence rate and improve survival following radical treatment by ensuring only patients with curable disease are referred. Local Anaesthetic Thoracoscopy (LAT) is the established gold-standard test for suspected pleural malignancy in patients with symptomatic effusion. We will prospectively evaluate LAT as a pleural staging tool in NSCLC and explore alternative mechanisms for poor outcomes using a range of translational end-points.

Ethics approval

Pending approval, West of Scotland Research Ethics Committee 1 (West of Scotland Research Ethics Service, Clinical Research and Development, West Glasgow Ambulatory Care Hospital, Dalnair Street, Glasgow G3 8SW; 0141 232 1807; WoSREC1@ggc.scot.nhs.uk)

Study design

Multi-centre observational study, incorporating a cross-sectional MRI sub-study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format please use contact details to request a copy of the participant information sheet

Condition

Lung Cancer

Intervention

STRATIFY is a study designed to evaluate the use of local anaesthetic thoracoscopy (LAT) in the staging and diagnosis of occult pleural metastases (OPM) in stage I-IIIa non-small cell lung cancer with miniPE. It is designed as a prospective, observational study. This means patients will be recruited to the trial at diagnosis and followed up to determine the prevalence of OPM and the effect diagnosis of these with LAT has on survival and choice of cancer treatment.
We will also be recruiting an eligible proportion of patients into an additional sub-study in order to determine how MRI markers compare to LAT in the detection of OPM in such patients.

Potentially eligible patients will be identified and assessed by the respiratory physician/site PI coordinating their care (or delegated members of the research team). Eligibility can be considered before completion of routine staging and formation of a oncology treatment plan. However, formal eligibility assessment must only occur after this process has been concluded, at a formal screening visit (Visit 1, Day 0). The study should only be introduced at earlier clinic visits, if eligibility is likely and this discussion is clinically appropriate. Potential participants will be given sufficient time (in their own judgement) to consider the commitment required to fulfil trial requirements, and to decide whether or not to participate. Where possible, patients will be given up to 24 hours, however due to the nature of the trial, and since some patients will be attending ‘one-stop’ clinics, same-day consent is permissible. Patients may choose to defer consent if they required additional time and will be offered a follow-up telephone call with a member of the study team for this purpose. This call will occur no later than 48 hours after Visit 1. In addition, all patients will be made aware that participation is voluntary and they may withdraw at any time without their standard care being affected. No screening activities related to the trial will be undertaken until informed consent has been obtained. Eligibility will be confirmed by a medical practitioner.

Patients will be recruited from to the MRI sub-study within the main study. Patients will be screened for eligibility and provided with an additional MRI sub-study PIS at Visit 1. Patients will be given sufficient time to consider participation (in their own judgement) and similar support will provided as in the main study, including the offer a follow-up telephone call with a member of the research time within 48 hours. Patients will be made fully aware that participation is voluntary and they can leave the trial at any time without their standard care being affected.

Once consented, admission to the sites's local unit will be arranged. Patients will normally be admitted through the medical day unit where baseline study assessment will be completed. At this time the patient will also be consented and prepared for their local anaesthetic thoracoscopy which will happen later that afternoon. This may include updated blood tests should there be no recent ones available.
LAT:
Local anaesthetic thoracoscopy involves the insertion of a camera through the chest wall in order to visualise the linings of the lung and take tissue samples (biopsies) for further investigation. LAT usually takes about one hour from start to finish.
You will be awake for this procedure but will be given sedation. A further ultrasound will be performed when you are positioned for the LAT to confirm thoracoscopy insertion site. This site will be marked and local anaesthetic injected to numb the area prior to starting.
Any pleural fluid surrounding the lung will be drained and sent for investigation and biopsies will be taken. On completion of the thoracoscopy, a chest drain will be inserted into the insertion site. To create more room to work during the thoracoscopy, air is allowed into the pleural cavity. This chest drain is therefore inserted to allow this air and any remaining fluid to escape. A post-thoracoscopy CXR is performed to assess position of this drain. Once all of this air has escaped and the lung has fully reinflated (as determined by a further CXR and drain inspection) this chest drain will be removed. Most commonly this is on the day of or the morning after LAT.

MRI Substudy:
Patients will attend the local site's imaging facility. An MRI safety checklist, +/- x-ray of the eye sockets to exclude metal fragments, will be completed by a member of the research imaging team. An MRI scan of the chest will then be performed. This involves lying flat inside the MRI scanner for 40-60 minutes. An injection of dye will be given through a drip during the scan and patients will also be asked to hold their breath for a short period a few times during the scan. This has been shown to be easily managed in the vast majority of patients with MPE in a similar protocol used in previous work within our unit (DIAPHRAGM MRI sub-study).

All patients will receive a follow up appointment around one week post LAT to discuss the results of any biopsies taken and the management plan based on these findings.
After this, all follow up will be decided by the team responsible for your routine care. As part of STRATIFY however your progress in terms of treatments given, evidence of recurrence and survival will be assessed every 2 months for the next 6 months. This will be done distantly and therefore will not involve any further clinical visits out with those planned as part of your routine standard care.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

The true prevalence of detectable OPM, as defined by the by the proportion of recruited patients with NSCLC cells in parietal pleural biopsies (pathology) or pleural fluid (cytology) obtained during Local Anaesthetic Thoracoscopy, at visit 3

Secondary outcome measures

1. LAT results, recorded as: OPM demonstrated/OPM not demonstrated (via pathology and cytology tests)
2. RFS, defined as the time from completion of NSCLC treatment (surgery, radical radiotherapy or radical chemo-radiotherapy) to documented recurrence of NSCLC or death from any cause. Treatment and Survival data will be collected from review of clinical notes at site and recorded in the study electronic CRF.
3. OS, defined as the time from NSCLC treatment to death from any cause. Survival data will be collected from review of clinical notes at site and recorded in the study electronic CRF.
4. LAT feasibility will be recorded as LAT complete/LAT incomplete (specify)/LAT not performed (specify). This information will be collected from review of clinical notes at site and recorded in the study electronic CRF, following the pre-LAT examinations such as US and x Ray and the LAT itself

5. MRI Sub-study Exploratory outcome measures:
This information will be collected from review of the relevant imaging clinical records at site :
5.1 Pleural MRI results (Presence or Absence of Pleural MRI-ECE or Pleural Pointillism) relative to LAT results
5.2 Systemic co-morbidity will be assessed using validated MRI end-points for cardiac dysfunction and body composition (including sarcopaenia, via muscle cross-sectional area) and related to LAT results, OS, PFS

Overall trial start date

01/09/2018

Overall trial end date

31/08/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Eligibility Criteria for the Main Study
1. Stage I-IIIA NSCLC, after completion of routine staging
2. Mini-PE, defined as an ipsilateral pleural effusion, which is ≤ 40 mm in max depth on axial CT scan and either:
2.1 Too small to safely aspirate after US assessment (level 1 operator judgement)
2.2 Cytology-negative after diagnostic aspiration
3. Performance Status 0-2
4. Radical treatment feasible (Surgery, Radical RT or chemo-RT) if OPM excluded by LAT (MDT judgement)
5. Aged 16 or over
6. Informed written consent
7. Willingness to comply with scheduled visits, study procedures and laboratory tests

Eligibility Criteria for the MRI sub-study
1. Registered to the main STRATIFY study
2. Informed written consent
3. Willingness to comply with scheduled visits, and study procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

96 patients, 42 of whom will also be recruited to the MRI sub-study

Participant exclusion criteria

Main study:
1. Any metastatic disease, including confirmed pleural metastases
2. Bilateral pleural effusions
3. Any contraindication to LAT, e.g.:
3.1 Absent lung-sliding on pleural ultrasound
3.2 Uncontrollable cough
3.3 Uncorrectable bleeding disorder

MRI Sub-study Exclusion Criteria
1. Any contraindication to MRI, including but not limited to:
1.1 Claustrophobia, pregnancy
1.2 Metallic foreign body
1.3 Pacemaker/implant
1.4 Allergy to Gadolinium contrast
1.5 eGFR <30 ml/min

Recruitment start date

01/06/2019

Recruitment end date

30/11/2020

Locations

Countries of recruitment

Australia, United Kingdom

Trial participating centre

NHS Greater Glasgow & Clyde, Queen Elizabeth Iniversity Hospital
1345 Govan Rd
Glasgow
G51 4TF
United Kingdom

Trial participating centre

University Hospital of South Manchester NHS Foundation Trust
Wythenshawe Hospital Southmoor Road
Manchester
M23 9LT
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital Headley Way Headington
OXFORD
OX3 9DU
United Kingdom

Trial participating centre

North Bristol NHS Trust, Southmead Hospital
Southmead Road Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Guy's and St Thomas NHS Foundation Trust
Trust Offices Guy's Hospital Great Maze Pond
London
SE1 7EH
United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Institute for Respiratory Health, Nedlands
Institute for Respiratory Health, Ground Floor E Block Hospital Avenue Nedlands
Perth
WA 6009
Australia

Sponsor information

Organisation

NHS Greater Glasgow & Clyde

Sponsor details

Research & Development
NHS Greater Glasgow and Clyde
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom

Sponsor type

Hospital/treatment centre

Website

n/a

Funders

Funder type

Government

Funder name

Chief Scientist Office

Alternative name(s)

CSO

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

31/08/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

05/04/2019: Trial’s existence confirmed by Scottish government