Condition category
Cancer
Date applied
23/08/2018
Date assigned
05/09/2018
Last edited
21/09/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Current plain English summary as of 29/08/2019:
Background and study aims
Mesothelioma is a cancer of the thin membrane that lines the chest. Around 2500 people in the UK are diagnosed with mesothelioma each year. Exposure to asbestos is the most common cause, although the cancer does not usually become apparent until 40-60 years after exposure. Anti-cancer drugs (chemotherapy) are usually given to help treat mesothelioma and sometimes lung-sparing surgery (pleurectomy decortication) is undertaken. However, it is not known if this surgery, in addition to chemotherapy, can increase survival and improve the quality of life for patients. The aim of this study (MARS 2) study is to compare combining this surgery and chemotherapy with chemotherapy alone with respect to overall survival, cost-effectiveness and quality of life at regular intervals for at least 2 years.

Who can participate?
Adults over the age of 16 who have been diagnosed with malignant pleural mesothelioma

What does the study involve?
We would like to assess whether surgery offers any benefit or not over standard clinical care in terms of improving survival and quality of life. Patients deemed suitable for surgery will be approached and participants will receive 2 cycles of chemotherapy and a computed tomography (CT) scan. If there is no significant worsening of cancer, participants will be randomly allocated to either surgery and up to 4 further cycles of chemotherapy or no-surgery and up to 4 further cycles of chemotherapy. All patients in the study will be closely monitored at several follow-up time points (6 weeks, 6 months, 12 months, 18 months and 24 months, and then at 6-monthly intervals until the end of the study) that will be scheduled after allocation to one of the study groups. At each of these time points up to 24 months patients will receive a phone call from the research team and be asked to complete some more quality of life questionnaires. After 24 months, patient will be sent a questionnaire, at 6-monthly intervals, to ascertain any new diagnoses and additional therapy received. MARS 2 also includes an Information study, where patients may be interviewed or have their consultations audio-recorded if they are happy with this. The aim of the Information study is to explore how a patient makes a decision to take part in research or not, with the overall aim of improving recruitment to clinical trials.

What are the possible benefits and risks of participating?
Participants may not personally gain any benefit from taking part in this study. The information we get from this study may help doctors decide how to treat malignant pleural mesothelioma in the future and how research is discussed with future patients.

Where is the study run from?
The MARS 2 study is being coordinated by the Clinical Trials and Evaluation Unit (CTEU) at the University of Bristol. There are currently 26 centres taking part in MARS 2.

When is the study starting and how long is it expected to run for?
February 2013 to September 2022

Who is funding the study?
National Institute for Health Research - Health Technology Assessment Programme (15/188/31) (UK)

Who is the main contact?
Prof. Eric Lim
e.lim@rbht.nhs.uk




Previous plain English summary:
Background and study aims
Mesothelioma is a cancer of the thin membrane that lines the chest. Around 2500 people in the UK are diagnosed with mesothelioma each year. Exposure to asbestos is the most common cause, although the cancer does not usually become apparent until 40-60 years after exposure. Anti-cancer drugs (chemotherapy) are usually given to help treat mesothelioma and sometimes lung-sparing surgery (pleurectomy decortication) is undertaken. However, it is not known if this surgery, in addition to chemotherapy, can increase survival and improve the quality of life for patients. The aim of this study (MARS 2) study is to compare combining this surgery and chemotherapy with chemotherapy alone with respect to overall survival, cost-effectiveness and quality of life at regular intervals for 2 years.

Who can participate?
Adults over the age of 16 who have been diagnosed with malignant pleural mesothelioma

What does the study involve?
We would like to assess whether surgery offers any benefit or not over standard clinical care in terms of improving survival and quality of life. Patients deemed suitable for surgery will be approached and participants will receive 2 cycles of chemotherapy and a computed tomography (CT) scan. If there is no significant worsening of cancer, participants will be randomly allocated to either surgery and 4 further cycles of chemotherapy or no-surgery and 4 further cycles of chemotherapy. All patients in the study will be closely monitored at several follow-up time points (6 weeks, 6 months, 12 months, 18 months and 24 months) that will be scheduled after allocation to one of the study groups. At each of these time points they will receive a phone call from the research team and be asked to complete some more quality of life questionnaires. MARS 2 also includes an Information study, where patients may be interviewed or have their consultations audio-recorded if they are happy with this. The aim of the Information study is to explore how a patient makes a decision to take part in research or not, with the overall aim of improving recruitment to clinical trials.

What are the possible benefits and risks of participating?
Participants may not personally gain any benefit from taking part in this study. We hope that any treatments received will help participants, however, this cannot be guaranteed. The information we get from this study may help doctors decide how to treat malignant pleural mesothelioma in the future and how research is discussed with future patients.
The possible risks of taking part include the standard risks of surgery (pain, bleeding and infection). Complications rarely develop after surgery but these can include kidney problems, heart attack and stroke. CT scans are considered safe; however, as with any injection, the injection aspect carries a slight risk of harm, including injury to a nerve, artery or vein, or a reaction to the material being injected. Occasionally, patients have mild reactions to the contrast agent and develop sneezing or hives. The staff of the X-ray department are trained to treat these reactions.

Where is the study run from?
Clinical Trials and Evaluation Unit (CTEU) at the University of Bristol and 22 centres across the UK

When is the study starting and how long is it expected to run for?
February 2013 to September 2022

Who is funding the study?
National Institute for Health Research - Health Technology Assessment Programme (15/188/31) (UK)

Who is the main contact?
Prof. Eric Lim
e.lim@rbht.nhs.uk

Trial website

http://cteu.bris.ac.uk/our-studies/?trialType=Thoracic-surgery#5202

Contact information

Type

Scientific

Primary contact

Prof Eric Lim

ORCID ID

Contact details

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom
0207 351 8591
e.lim@rbht.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT02040272

Protocol/serial number

15/188/31

Study information

Scientific title

Mesothelioma and Radical Surgery 2: a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

Acronym

MARS 2

Study hypothesis

(Extended) pleurectomy decortication and chemotherapy is superior to chemotherapy alone with respect to overall survival.

Ethics approval

London - Camberwell St Giles Research Ethics Committee, 28/10/2017, REC ref: 13/LO/1481

Study design

Interventional multi-centre open-label parallel two-group pragmatic randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Pleural mesothelioma

Intervention

Current interventions as of 29/08/2019:
Participants will be randomly allocated to either the intervention group or the control group. Randomisation will be carried out electronically using a secure web-based system (Sealed Envelope (https://sealedenvelope.com)). The allocation will not be revealed until sufficient information to uniquely identify the participant has been entered. Minimisation (with a random component) for selected baseline variables (age, performance status and cell type) that influence survival, in addition to stratification by centre to ensure that the cohorts are as balanced as possible, will be applied. Randomisation will be carried out by a member of the research team at the medical centre after the participant has received 2 cycles of chemotherapy, and had a further CT scan to confirm eligibility (i.e. resectable disease).
Participants in both groups will receive an initial 2 cycles of standard chemotherapy (platinum and pemetrexed), which will take around 3 weeks per cycle.

The experimental intervention group will receive chemotherapy and surgery for mesothelioma. Pleurectomy decortication surgery involves removal of the lining of the chest wall and lining of the lung, possibly also with the sac around the heart and/or diaphragm (“extended”) as required to achieve complete tumour removal but leaving the lung in-situ. The decision to perform pleurectomy decortication or extended pleurectomy decortication will be made by the surgeon based on surgical findings. Patients in this group will usually be in hospital for approximately 10-14 days, and the post-operative recovery period is usually 3 weeks. Participants will then receive up to 4 cycles of platinum and pemetrexed chemotherapy.

The control group will receive a further 4 cycles of the standard chemotherapy above.

Participants in both groups will be followed up after 6 weeks, and 6, 12, 18 and 24 months, and then every 6 months until the end of the study. Participants who have had surgery will also attend the surgical centre for a post-operative check, usually 3-6 weeks post-surgery.
MARS 2 also includes an Information study called the QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment and informed consent by understanding and addressing recruitment challenges across the centres in a tailored and flexible way. Patients will have the option of having their discussions with health professionals about MARS2 audio-recorded, along with an optional interview with a researcher to understand their perspectives on the study, the treatment offered, and why they made the decision they did. Interviews will also be undertaken with study staff and recruiters, along with scrutiny of screening logs and patient-facing documents. This data will be combined to identify key recruitment challenges. Having identified key difficulties, tailored strategies can then be offered to minimise these, which may include recruiter training, and suggestions to change patient pathways and patient-facing documents. Recruitment rates will be mapped against the timings of strategies and evidence of improvements in informed consent will be sought to indicate evidence of effectiveness.




Previous interventions:
Participants will be randomly allocated to either the intervention group or the control group. Randomisation will be carried out electronically using a secure web-based system (Sealed Envelope (https://sealedenvelope.com)). The allocation will not be revealed until sufficient information to uniquely identify the participant has been entered. Minimisation (with a random component) for selected baseline variables (age, performance status and cell type) that influence survival, in addition to stratification by centre to ensure that the cohorts are as balanced as possible, will be applied. Randomisation will be carried out by a member of the research team at the medical centre after the participant has received 2 cycles of chemotherapy, and had a further CT scan to confirm eligibility (i.e. resectable disease).
Participants in both groups will receive an initial 2 cycles of standard chemotherapy (platinum and pemetrexed), which will take around 3 weeks per cycle.
The experimental intervention group will receive chemotherapy and surgery for mesothelioma. Pleurectomy decortication surgery involves removal of the lining of the chest wall and lining of the lung, possibly also with the sac around the heart and/or diaphragm (“extended”) as required to achieve complete tumour removal but leaving the lung in-situ. The decision to perform pleurectomy decortication or extended pleurectomy decortication will be made by the surgeon based on surgical findings. Patients in this group will usually be in hospital for approximately 10-14 days, and the post-operative recovery period is usually 3 weeks. Participants will then receive up to 4 cycles of platinum and pemetrexed chemotherapy within 12 weeks of the operation.
The control group will receive a further 4 cycles of the standard chemotherapy above.
Participants in both groups will be followed up after 6 weeks, and 6, 12, 18 and 24 months. Participants who have had surgery will also attend the surgical centre for a post-operative check, usually 3-6 weeks post-surgery.
MARS 2 also includes an Information study called the QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment and informed consent by understanding and addressing recruitment challenges across the centres in a tailored and flexible way. Patients will have the option of having their discussions with health professionals about MARS2 audio-recorded, along with an optional interview with a researcher to understand their perspectives on the study, the treatment offered, and why they made the decision they did. Interviews will also be undertaken with study staff and recruiters, along with scrutiny of screening logs and patient-facing documents. This data will be combined to identify key recruitment challenges. Having identified key difficulties, tailored strategies can then be offered to minimise these, which may include recruiter training, and suggestions to change patient pathways and patient-facing documents. Recruitment rates will be mapped against the timings of strategies and evidence of improvements in informed consent will be sought to indicate evidence of effectiveness.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Current primary outcome measure as of 29/08/2019:
Survival up to the end of the study, determined by confirmation of death by the trial site

Previous primary outcome measure:
Survival up to 2 years after randomisation, determined by confirmation of death by the trial site

Secondary outcome measures

Current secondary outcome measures:
1. Progression-free survival to the end of the study (minimum of 2 years after randomisation into the study), assessed by recurrence, which is collected using purpose-designed Case Report Forms and questionnaires at each follow-up appointment (6 weeks and 6, 12, 18 and 24 months after treatment and every 6 months thereafter until the end of the study)
2. Serious adverse health events 2 years after randomisation into the study, collected using purpose-designed Case Report Forms at each follow-up appointment (up to 24 months)
3. Health-related quality of life, assessed after 6 weeks and 6, 12, 18 and 24 months after randomisation into the study using:
3.1. European Organization for Research and Treatment Core Quality of Life Questionnaire (EORTC QLQ-C30)
3.2. EuroQol-5D-5L (EQ-5D-5L)
4. Resource and health service use, collected using purpose-designed Case Report Forms at each follow-up appointment (up to 24 months) and during initial surgical admission for the intervention group


Previous secondary outcome measures:
1. Progression-free survival 2 years after randomisation into the study, assessed by recurrence, which is collected using purpose-designed Case Report Forms at each follow-up appointment (6 weeks and 6, 12, 18 and 24 months after treatment)
2. Serious adverse health events 2 years after randomisation into the study, collected using purpose-designed Case Report Forms at each follow-up appointment
3. Health-related quality of life, assessed after 6 weeks and 6, 12, 18 and 24 months after randomisation into the study using:
3.1. European Organization for Research and Treatment Core Quality of Life Questionnaire (EORTC QLQ-C30)
3.2. EuroQol-5D-5L (EQ-5D-5L)
4. Resource and health service use, collected using purpose-designed Case Report Forms at each follow-up appointment and during initial surgical admission for the intervention group

Overall trial start date

21/02/2013

Overall trial end date

30/09/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Patient may enter study if ALL of the following apply:
1. Aged 16 years or older
2. Tissue (cytology or histology) confirmed epithelioid, sarcomatoid or biphasic mesothelioma*
3. Disease confined to one hemi-thorax based on CT assessment
4. Disease deemed surgically resectable**
5. Fit for surgery**
6. Capacity to provide written informed consent to participate in the trial

*The “diagnosis” of mesothelioma is based on cytology and / or histopathology results as reviewed by MDT to be of sufficient certainty to recommend chemotherapy as treatment.
**To be confirmed by a surgeon at a MARS 2 surgical site (added 29/08/2019)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

328

Participant exclusion criteria

Current inclusion criteria as of 29/08/2019:
Patient may not enter study if ANY of the following apply:
1. Severe shortness of breath (this is defined as an Eastern Cooperative Oncology Group (ECOG) status >= 2, or if lung function tests are performed: pre-operative forced expiratory volume after one second (FEV1) or transfer factor of the lung for carbon monoxide (TLco) less than 20%);
2. Serious concomitant disorder that would compromise participant safety during surgery (e.g. evidence of end organ failure)
3. Severe heart failure (this is defined as NYHA III or IV or if an echocardiogram is performed an ejection fraction less than 30%)
4. End stage kidney failure requiring dialysis
5. Liver failure (e.g. encephalopathy and/or coagulation abnormalities)
6. Prisoner
7. Patient lacks capacity to consent
8. Existing co-enrolment in another interventional clinical trial that aims to improve survival


Previous exclusion criteria:
Patient may not enter study if ANY of the following apply:
1. Severe shortness of breath (Eastern Cooperative Oncology Group (ECOG) status >= 2, pre-operative forced expiratory volume after one second (FEV1) or transfer factor of the lung for carbon monoxide (TLco) less than 20%);
2. Serious concomitant disorder that would compromise participant safety during surgery (e.g. evidence of end organ failure)
3. Severe heart failure (EF less than 30% by echocardiogram)
4. End stage kidney failure requiring dialysis
5. Liver failure (e.g. encephalopathy and/or coagulation abnormalities)
6. Prisoner
7. Patient lacks capacity to consent
8. Co-enrolment in another interventional clinical trial

Recruitment start date

05/05/2015

Recruitment end date

31/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Trial participating centre

Barts Health NHS Trust
Royal London Hospital, Whitechapel Road, Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Cardiff & Vale University Health Board
University Hospital of Wales, Health Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

The Clatterbridge Cancer Centre NHS Foundation Trust
Clatterbridge Road, Bebington
Wirral
CH63 4JY
United Kingdom

Trial participating centre

Colchester Hospital University NHS Foundation Trust
Colchester General Hospital, Turner Road, Colchester
Essex
CO4 5JL
United Kingdom

Trial participating centre

Derby Teaching Hospitals NHS Foundation Trust
Royal Derby Hospital, Uttoxeter Road
Derby
D22 3NE
United Kingdom

Trial participating centre

Golden Jubilee National Hospital
Beardmore Street Clydebank
Glagow
G81 4HX
United Kingdom

Trial participating centre

Greater Glasgow Health Board
JB Russell House, Gartnavel Royal Hospital, 1055 Great Western Road
Glasgow
G12 0XH
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
Trust Headquarters, Beckett Street, St. James's University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

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

Trial participating centre

Papworth Hospital NHS Foundation Trust
Papworth Everard
Cambridge
CB23 3RE
United Kingdom

Trial participating centre

Peterborough and Stamford Hospitals NHS Foundation Trust
Edith Cavell Campus, Bretton Gate, Bretton
Peterborough
PE3 9GZ
United Kingdom

Trial participating centre

Aneurin Bevan University Health Board
Aneurin Bevan University Local Health Board Headquarters, Mamhilad, Park Estate, Pontypool
Torfaen
NP4 0YP
United Kingdom

Trial participating centre

Royal Marsden NHS Foundation Trust
Fullham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
Trust Headquarters, 8 Beech Hill Road
Sheffield
S10 2SB
United Kingdom

Trial participating centre

South Tees Hospitals NHS Foundation Trust
The James Cook University Hospital, Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

South Tyneside NHS Foundation Trust
Harton Lane
South Shields
NE34 0PL
United Kingdom

Trial participating centre

Royal Wolverhampton NHS Trust
New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

North Bristol NHS Trust
Trust Headquarters, Southmead hospital, Southmead Road, Westbury on Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospitals NHS Foundation Trust
Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

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

Trial participating centre

Barking, Havering and Redbridge University Hospitals NHS Trust
Queen's Hospital, Rom Valley Way, Romford
Essex
RM7 0AG
United Kingdom

Trial participating centre

Guy’s and St Thomas’ NHS Foundation Trust
Guy’s Hospital, Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Maidstone and Tunbridge Wells NHS Trust
Maidstone Hospital Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital Birmingham Mindelsohn Way
Birmingham
B15 2GW
United Kingdom

Sponsor information

Organisation

Royal Brompton and Harefield NHS Foundation Trust

Sponsor details

Sydney Street
London
SW3 6NP
United Kingdom
0207 351 8736
p.pettersson@rbht.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.rbht.nhs.uk/research

Funders

Funder type

Not defined

Funder name

Health Technology Assessment Programme

Alternative name(s)

HTA

Funding Body Type

unknown

Funding Body Subtype

Location

Funder name

Cancer Research UK

Alternative name(s)

Funding Body Type

unknown

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The findings will be disseminated by usual academic channels, i.e. presentation at international meetings, as well as by peer-reviewed publications (including a full report to the NIHR-HTA programme) and through patient organisations and newsletters to patients, where available.

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

Intention to publish date

30/09/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2020 protocol in https://pubmed.ncbi.nlm.nih.gov/32873681/ (added 04/09/2020)

Publication citations

Additional files

Editorial Notes

21/09/2020: The recruitment end date was changed from 30/09/2020 to 31/12/2020. 04/09/2020: Publication reference added. 29/08/2019: The following changes were made to the trial record: 1. The plain English summary was updated. 2. The interventions were updated. 3. The primary outcome measure was changed. 4. The secondary outcome measures were changed. 5. The inclusion criteria were added to. 6. The exclusion criteria were changed. 7. The trial participating centres were added: Oxford University Hospitals NHS Foundation Trust, Maidstone and Tunbridge Wells NHS Trust, University Hospitals Birmingham NHS Foundation Trust.