Radical management of advanced non-small cell lung cancer

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-further-treatment-after-initial-treatment-for-advanced-non-small-cell-lung-cancer

Background and study aims
Lung cancer is the most common cause of cancer death worldwide, and the majority of patients in the UK present with advanced disease. One-year survival is improving but remains low at 37% despite new treatments which now form the current standard of care for advanced lung cancer. Although these new treatments are very good, some cancer persists in most patients after treatment (termed ‘residual cancer’) and little is known about how best to deal with it. As such, management of residual advanced lung cancer varies across the UK, with some patients receiving only symptom management while others go on to have treatment in the form of surgery, radiotherapy and/or ablation with the aim to remove all remaining cancer within the lung and throughout the body. Collectively, these treatments are known as local consolidative treatment (LCT). LCT is intensive, impacts quality of life and is expensive but most importantly, it is not known whether it results in a better outcome for patients.
The aim of this study is to find out whether LCT alongside symptom management is worthwhile (or not) for patients with residual advanced lung cancer. Patients who agree to join the study will be divided into two equal-sized groups. One group will receive LCT alongside symptom management and the other group will receive symptom management alone. The study will compare the two groups' overall survival and quality of life, as well as the cost-effectiveness for the NHS.

Who can participate?
Patients aged 18 years and over with advanced stage (stage IV) non-small cell lung cancer who have undergone a course of initial systemic anti-cancer treatment.

What does the study involve?
After reading the study information and having discussions with the research team if necessary, participants will be asked to sign a consent form to document their willingness to take part in the study. As it is not known if it is better to have LCT alongside symptom management or have symptom management alone, the type of treatment a participant receives will be allocated through a process called randomisation (neither the participant, doctors/nurses nor the research team can choose which group a participant goes into). Each person has an equal chance of being in each group. The two groups a participant could be randomly allocated into are:
1. LCT (made up of surgery, radiotherapy and/or ablation) in addition to symptom management
2. Symptom management alone.
If a participant is allocated to receive LCT, their care team will decide on the most clinically appropriate type of treatment, in the form of surgery, radiotherapy and/or ablation for each current cancer site and any additional new sites that may arise. Where appropriate treatments to improve symptoms may also be given.
If a participant is allocated to receive symptom management alone, their care team will decide on the most clinically appropriate treatment(s).
Participants will also be asked to complete some questionnaires, once before they are randomised into the study; at 6 weeks after randomisation; and then every 6 months until the end of the study, for a minimum of 2 years and a maximum of 5 years. These questionnaires will give the study team information about a participant's quality of life and overall wellbeing.

What are the possible benefits and risks of participating?
It is hoped that any treatment a participant receives will help them, however this cannot be guaranteed. The information gained from the study may help improve the treatment of people with advanced lung cancer in the future.
The treatment received as part of either LCT or symptom management may result in a participant experiencing some side effects which will be explained by the treating clinician and also listed in the patient information sheet. The study may also result in increased exposure to ionising radiation which can also cause short-term side effects. Ionising radiation may also cause cancer many years or decades after the exposure however the chance of this happening to people with this clinical condition is extremely small.

Where is the study run from?
Bristol Trials Centre at the University of Bristol (UK)

When is the study starting and how long is it expected to run for?
August 2021 to February 2027

Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)

Who is the main contact?
Miss Chloe Beard, ramon-study@bristol.ac.uk

Study website

https://bristoltrialscentre.blogs.bristol.ac.uk/details-of-studies/ramon/

Type

Principal Investigator

Contact name

Prof Eric Lim

ORCID ID

Contact details

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom
+44 (0)2073518591
e.lim@rbht.nhs.uk

Type

Scientific

Contact name

Prof Eric Lim

ORCID ID

Contact details

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom
+44 (0)2073518591
e.lim@rbht.nhs.uk

Type

Public

Contact name

Miss Chloe Beard

ORCID ID

Contact details

Bristol Trials Centre
University of Bristol
1-5 Whiteladies Road
Clifton
Bristol
BS8 1NU
United Kingdom
+44 (0)117 455 6706
ramon-study@bristol.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

308485

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRAS 308485, NIHR131306, CPMS 53678

Scientific title

Multi-modality local consolidative treatment versus conventional care of advanced lung cancer after first-line systemic anti-cancer treatment: a multi-centre randomised controlled trial with an internal pilot

Acronym

RAMON

Study hypothesis

Local consolidative treatment (LCT) in addition to maintenance systemic anti-cancer treatment and/or supportive care (conventional care) improves overall survival by an absolute 20% at 2 years compared to conventional care alone.

Ethics approval(s)

Approved 06/10/2022, West of Scotland REC 3 (Research Ethics, Ward 11, Dykebar Hospital,
Grahamston Road, Paisley, PA2 7DE, United Kingdom; +44 (0)141 314 0212; WoSREC3@ggc.scot.nhs.uk), ref: 22/WS/0121

Study design

Pragmatic multi-centre randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Stage IV advanced lung cancer

Intervention

RAMON is a pragmatic, multi-centre randomised controlled trial (RCT) in NHS hospitals, with an internal pilot phase and active follow-up for a minimum of 2 years. The full RCT will evaluate the acceptability, effectiveness and cost-effectiveness of Local Consolidative Treatment (LCT) alongside symptom management versus symptom management alone, after first-line treatment for advanced lung cancer. Recruiting sites will be supported with an integrated QuinteT Recruitment Intervention (QRI) and patients will be followed up for quality of life and resource use outcomes at various points over a minimum of a 2-year period.

Patients with stage IV advanced lung cancer who have undergone a course of initial systemic anti-cancer treatment and consent to participate in the study will be randomised using a secure internet-based randomisation system into one of two groups:
1. Local consolidative treatment (LCT) alongside symptom management treatment
2. Symptom management treatment alone

For participants randomised to receive LCT, treating clinicians will decide the most clinically appropriate treatment in the form of surgery, radiotherapy or ablation with radical intent (prolonging survival). Each current disease site and any new disease sites that may arise throughout the duration of the study will be treated accordingly.

For participants who are randomised to receive symptom management alone, treating clinicians will decide the most clinically appropriate treatment with the intention of relieving symptoms only.

Intervention type

Other

Primary outcome measure

Overall survival, defined as date of randomisation to death from any cause (minimum follow-up 2 years after randomisation)

Secondary outcome measures

1. Disease progression-free survival (PFS), defined as the time from randomisation to documented disease progression, as evaluated by local site radiologist from CT or PET/CT scan (e.g. CT of the head, chest, abdomen, pelvis and other anatomical sites); bone scan or MRI, carried out as part of the patients’ standard care (minimum follow-up 2 years after randomisation) or death from any cause
2. Serious adverse health events recorded using safety reporting processes and data collection forms from randomisation to the end of the study (minimum of 2 years)
3. Patient-reported HRQoL measured using the European Organisation For Research and Treatment of Cancer’s Quality of Life Questionnaire-C30 (EORTC QLQ-C30) from randomisation to the end of the study (minimum of 2 years)
4. Health-related quality of life measured using the European Organisation For Research and Treatment of Cancer’s Quality of Life Questionnaire-LC13 (EORTC QLQLC13) to the end of the study (minimum of 2 years)
5. Health-related quality of life measured using the EQ-5D-5L questionnaire (EuroQol EQ-5D-5L) to the end of the study (minimum of 2 years)

Overall study start date

01/08/2021

Overall study end date

28/02/2027

Reason abandoned (if study stopped)

Participant inclusion criteria

1. 18 years of age or over
2. Tissue confirmed non-small cell lung cancer pre-treatment clinical stage IV
3. Lung cancer treatment naïve prior to initial study systemic anti-cancer treatment
4. Completed standard of care systemic anti-cancer treatment
5. Performance status 0 (i.e. asymptomatic) or performance status 1 (i.e. symptomatic but completely ambulatory) as per Eastern Cooperative Oncology Group (ECOG) definitions
6. LCT eligible disease, defined as all disease sites amenable to radical treatment (e.g. surgery, radiotherapy or ablation)

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

244

Total final enrolment

11

Participant exclusion criteria

1. Serious concomitant disorder that would compromise patient safety during LCT
2. Complications from initial systemic anti-cancer treatment that precludes maintenance systemic anti-cancer treatment
3. Patient unable/unwilling to adhere to study procedures
4. Patient unable to give written informed consent
5. Women who are pregnant or breast feeding
6. Co-enrolment in another trial if either: interventional trial that aims to improve survival, not permitted by other trial, would result in too much patient burden

Recruitment start date

21/02/2023

Recruitment end date

12/01/2024

Countries of recruitment

England, Scotland, United Kingdom, Wales

Study participating centre

The Royal Brompton & Harefield Hospitals
Royal Brompton Hospital and Harefield hospitals
Sydney Street
London
SW3 6NP
United Kingdom

Study participating centre

Chelsea and Westminster Hospital NHS Foundation Trust
Chelsea & Westminster Hospital
369 Fulham Road
London
SW10 9NH
United Kingdom

Study participating centre

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

Study participating centre

Imperial College Healthcare NHS Trust
The Bays
St Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom

Study participating centre

University Hospitals of Derby and Burton NHS Foundation Trust
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Study participating centre

Nottingham University Hospitals NHS Trust - City Campus
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Study participating centre

New Cross Hospital
Wolverhampton Rd
Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Study participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2GW
United Kingdom

Study participating centre

University Hospitals Plymouth NHS Trust
Derriford Hospital
Derriford Road
Derriford
Plymouth
PL6 8DH
United Kingdom

Study participating centre

University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Study participating centre

St. Bartholomews Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Study participating centre

Southend University Hospital
Prittlewell Chase
Westcliff-on-sea
SS0 0RY
United Kingdom

Study participating centre

Clatterbridge Cancer Centre
Clatterbridge Hospital
Clatterbridge Road
Wirral
CH63 4JY
United Kingdom

Study participating centre

Clatterbridge Cancer Centre - Liverpool
65 Pembroke PLACE
Liverpool
L7 8YA
United Kingdom

Organisation

Royal Brompton Hospital

Sponsor details

Royal Brompton & Harefield Hospitals
Sydney Street
London
SW3 6NP
England
United Kingdom
+44 (0)2073518109
i.jakupovic@rbht.nhs.uk

Sponsor type

Hospital/treatment centre

Website

https://www.rbht.nhs.uk/our-hospitals

ROR

https://ror.org/00cv4n034

Funder type

Government

Funder name

National Institute for Health and Care Research

Alternative name(s)

National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

A detailed manuscript and full report will be provided to NIHR HTA for publication in the HTA
Journal. The research findings are also planned to be published in high profile peer reviewed journals and wherever possible, the findings will be published in open access journals. In addition, findings will be disseminated through presentations at national and international meetings and through educational activities to ensure maximum dissemination of the findings.

Intention to publish date

31/07/2027

Individual participant data (IPD) sharing plan

Data will not be made available for sharing until after publication of the main results of the study unless agreed by the Chief Investigator/Trial Management Group on a case by case basis. Thereafter, anonymised individual patient data will be made available for secondary research, conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the MRC Policy on Data Sharing regarding scientific quality, ethical requirements and value for money. A minimum requirement with respect to scientific quality will be a publicly available pre-specified protocol describing the purpose, methods and analysis of the secondary research, e.g. a protocol for a Cochrane systematic review. Anonymised consultation data collected through the QinteT Recruitment Intervention may be used for training and for cross-trial synthesis once trial recruitment is complete and the report on this element of the research is completed. Please contact Prof Eric Lim using the following email: ramon-study@bristol.ac.uk

IPD sharing plan summary

Available on request

Study outputs