Mesothelioma and Radical Surgery 2

Study Overview
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Brief Summary
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Mesothelioma is a cancer of the thin membrane that lines the chest and abdomen. Around 2500 people in the UK are diagnosed with mesothelioma each year and the median survival is approximately 8.5 months. 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 the MARS2 study is to compare surgery - (extended) pleurectomy decortication - with no surgery with respect to overall survival, cost-effectiveness and quality of life. Patients will be followed up by phone at regular intervals for 2 years. Patients will be asked to complete and return a Quality of Life Questionnaire at these time points. MARS 2 also includes an optional 'Information study', where consenting patients may be interviewed or have their consultations audio-recorded. 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.

Official Title
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Mesothelioma and Radical Surgery 2: a Multicentre Randomised Trial Comparing (Extended) Pleurectomy Decortication Versus no (Extended) Pleurectomy Decortication for Patients With Malignant Pleural Mesothelioma (Mars 2).

Conditions
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Mesothelioma

Intervention / Treatment
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* Procedure: (Extended) pleurectomy decortication


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 16 years of age or over Tissue (cytology or histology) confirmed epithelioid, sarcomatoid or biphasic mesothelioma Disease confined to one hemi-thorax based on CT assessment Disease deemed surgically resectable Fit for surgery Capacity to provide written informed consent to participate in the trial Exclusion criteria: 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%) Serious concomitant disorder that would compromise participant safety during surgery (e.g. evidence of end organ failure) Severe heart failure (this is defined as NYHA III or IV or if an echocardiogram is performed an ejection fraction less than 30%) End stage kidney failure requiring dialysis Liver failure (e.g. encephalopathy and/or coagulation abnormalities) Prisoner Patient lacks capacity to consent Existing co-enrolment in another interventional clinical trial that aims to improve survival

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery<br>(Extended) pleurectomy decortication | Procedure: (Extended) pleurectomy decortication<br> <br> |
| No Intervention: no surgery<br>no surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | The time from randomisation to death will be measured and date of death will be collected on purposely designed case report forms. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival to two years |  | 24 months | 
| Serious adverse health events to two years after randomisation |  | 24 months | 
| Health Related Quality of Life: EORTC QLQ-C30 (questionnaire) to two years | 3 types of scales. Functioning scales which include physical functioning, role functioning, emotional function, cognitive functioning and social functioning. Symptom scales which include fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties. An overall global health status/QoL All scales range between 0 and 100. For functioning scales, a high score indicates a high level of functioning. Similarly, a high global health status/QoL score indicates a high quality of life. For symptom scales, a high score indicates a high level of symptoms. | 24 months | 
| Resource and health service use to two years and during initial surgical admission for surgical arm |  | 24 months and during initial surgical admission for surgical arm | 
| Health Related Quality of Life: EQ-5D-5L (questionnaire) to two years | subscales: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. These range from 1-5. subscales mobility, self-care, usual activities, pain/discomfort, anxiety/depression are combined to calculate an overall index score which ranges from -0.59 to 1. A higher score indicates better quality of life | 24 Months | 
| Health Related Quality of Life: EQ-5D-5L (questionnaire) to two years | VAS (visual analogue scale) score. Ranges from 0 to 100. A higher score indicates better quality of life | 24 months |