Malignant Mesothelioma - Can we Improve Quality of Life

Study Overview
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Brief Summary
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Patients with malignant pleural mesothelioma (MPM) frequently have significant physical symptoms, with up to 92% of patients complaining of three or more symptoms at presentation. Such symptom scores are similar to those reported in advanced non small cell lung cancer (NSCLC) and have been demonstrated to correlate with interference with activity and worse quality of life (QOL). Several studies have reported that baseline Quality of Life (QOL) is a significant prognostic factor for survival in NSCLC patients. In 2010, a non-blinded randomised controlled trial of 151 patients in the United States (US) demonstrated an improved QOL, fewer depressive symptoms and improved survival with early, regular specialist palliative care team (SPCT) involvement in addition to their routine care. The RESPECT-Meso study will examine the effect on quality of life following early Specialist Palliative Care (SPC) involvement for Regular Early Symptom Control Treatment (RESSCT) in addition to routine care in patients with newly diagnosed MPM in the United Kingdom (UK).

Detailed Description
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The purpose of this study is to examine if regular early Specialist Symptom Control Treatment (SSCT) involvement in mesothelioma patients can improve patients' and carers' quality of life (QOL) during their illness. Mesothelioma is a cancer of the lining around the chest wall which is caused by asbestos exposure. The UK has the highest death rate from mesothelioma in the world and mesothelioma will soon account for approximately 1 in 170 of all deaths in the UK. At present, there is no cure. About a third of patients have chemotherapy, which can prolong how long patients live ('survival') by a few months. For many patients, doctors can only offer treatment of symptoms from the cancer, rather than treating the cancer itself. For most patients, survival is usually between 8-12 months. Mesothelioma causes many symptoms including breathlessness, chest pain, weight loss and fatigue. Specialist Palliative Care (SPC) medicine doctors and nurses are specialists in treating symptoms due to life limiting illness. They also provide emotional support for patients and carers. The current practice in the UK is to involve SPC towards the end of a patient's life. A recent study from America examining lung cancer patients showed that involving SPC early in a patient's treatment improved patients' QOL during their illness, and also their survival. Until a cure for, or significant advance in the treatment of, MPM becomes available, attempts to improve the QOL of patients and carers will remain the primary goal of teams managing their care. Recent research examining NSCLC and early SPCT intervention by Temel et al demonstrated that such a novel approach is plausible, possible and effective in improving patients' QOL. This report demonstrated a survival benefit of 2.7 months; if a new chemotherapy drug were to demonstrate such an effect, it would likely be considered a significant breakthrough in the treatment of MPM. Current practice in the UK is to involve SPC towards the final months, and perhaps weeks, of a life-limiting illness. Therefore, the regular early SSCT intervention is well-placed to demonstrate any effects from the proposed intervention. This comprehensive, randomised, multicentre study will examine both patient and caregiver QOL, and the healthcare economic consequences of providing such an intervention. The results of such will be widely applicable to many institutions and patients throughout the UK. This study will randomly divide patients to either all normal treatment and support ('usual care', as is always offered), or usual care and regular SPC consultations from the time of diagnosis. No treatments will be withheld; this study is providing additional support to patients and their families. Patients will be asked to complete a set of questionnaires at the start of the study, and then monthly for up to 6 months. Carers will also complete a set of questionnaires at the start of the study and then at 3 and 6 months. Reported QOL and survival between the two groups will then be compared.

Official Title
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A Multicentre, Non-blinded, Randomised Controlled Trial to Assess the Impact of Regular Early SPEcialist Symptom Control Treatment on Quality of Life in Malignant Mesothelioma - RESPECT-Meso

Conditions
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Mesothelioma, Malignant

Intervention / Treatment
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* Other: Regular Early Specialist Symptom Control Treatment (RESSCT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmation of malignant pleural mesothelioma (MPM) Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1. (Asymptomatic patients score 0; symptomatic but ambulatory patients score 1) The diagnosis of MPM received within the last 6 weeks Ability to provide written informed consent in English and comply with trial procedures Exclusion Criteria: Other known malignancy within 5 years (excluding localised squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, grade III and low grade prostate cancer (Gleason score <5, with no metastases)). Significant morbidity which the lead physician (or MDT) feel will unduly confound or influence QOL. Those patients the MDT judge require referral to the SPCT at the point of diagnosis. Concurrent, or less than 3 months, since participation in another non-mesothelioma clinical trial that may affect QOL. Participation in a concurrent mesothelioma trial, within 12 weeks after randomisation, that may affect QOL. Referral at the time of recruitment for cytoreductive, tumour de-bulking, radical decortication or extrapleural pneumonectomy surgery for MPM. (Video Assisted Thoracoscopic Surgery or 'mini' thoracotomy for pleurodesis and diagnosis attempts are permissible.) Chemotherapy treatment for MPM initiated prior to consent. A significant history of depression / anxiety / psychiatric illness requiring specialist hospital care within the last 12 months.

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RESSCT plus Standard Care/Therapy<br>Regular Early Specialist Symptom Control Treatment (RESSCT) and Standard Therapy. Participants will be seen within three weeks of randomisation by the Specialist Palliative Care Team (SPCT), (regardless of, and in addition to, all other treatments being offered). The initial meeting will be an approximately 1 hour consultation with a member of the Specialist Palliative Care team. This may be either a Consultant or Specialist Palliative Care Clinical Nurse Specialist (SPCCNS). Patients will then continue to be seen regularly on at least a 4 weekly basis (regardless of other treatments, interventions and symptoms) by a member of the SPCT, with consultations lasting approximately 30 minutes. These monthly reviews will continue until end of trial (EOT) or patient death. | Other: Regular Early Specialist Symptom Control Treatment (RESSCT)<br>* Participants will be seen within three weeks of randomisation by the Specialist Palliative Care Team (SPCT), (regardless of, and in addition to, all other treatments being offered). The initial meeting will be an approximately 1 hour consultation with a member of the Specialist Palliative Care team. This may be either a Consultant or Specialist Palliative Care Clinical Nurse Specialist (SPCCNS). Patients will then continue to be seen regularly on at least a 4 weekly basis (regardless of other treatments, interventions and symptoms) by a member of the SPCT, with consultations lasting approximately 30 minutes. These monthly reviews will continue until end of trial (EOT) or patient death.<br>* Other names: Regular Early Specialist Palliative Care;|
| No Intervention: Standard Care/Therapy<br>The standard care/therapy control group will continue to receive all appropriate, standard treatment for Malignant Pleural Mesothelioma (MPM) currently available to them and will be initiated by the patient's General Practitioner (GP), the cancer MDT or lead respiratory physician as required. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EORTC C-30 Quality of Life | The primary objective of this randomised controlled study is to assess the impact of regular early specialist symptom control treatment (SSCT) involvement on global quality of life (QOL) in patients recently diagnosed with malignant pleural mesothelioma (MPM) 12 weeks post randomisation as compared to standard care. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life (HRQoL) in Patients | The following questionnaire will be used to measure HRQoL in patients; - EORTC C-30 This will be completed at baseline & 24 weeks following randomisation. | Baseline & 24 weeks | 
| Health Related Quality of Life (HRQoL) in Patients | The following questionnaire will be used to measure HRQoL in patients; - EORTC LC-13 This will be completed at baseline, 12 & 24 weeks following randomisation. | Baseline 12 & 24 weeks | 
| Health Related Quality of Life (HRQoL) in Patients | The following questionnaire will be used to measure HRQoL in patients; - EuroQol-5 Dimension questionnaire (EQ-5D) This will be completed at baseline, 12 & 24 weeks following randomisation. | Baseline, 12 & 24 weeks | 
| Patient Mood | The following questionnaire will be used to measure mood in patients; - Global Health Questionnaire (GHQ) 12 This will be completed at baseline, 12 & 24 weeks following randomisation. | Baseline, 12 & 24 weeks | 
| Primary Caregiver Health Related Quality of Life (HRQoL) | The following questionnaires will be used to measure HRQoL in primary caregivers; - Short Form 36 item questionnaire (SF-36) This will be completed at baseline, 12 & 24 weeks following randomisation and subsequently at 24 week post patient mortality. | Baseline, 12 & 24 weeks & 24 weeks post mortality of the patient. | 
| Primary Caregiver Mood | The following questionnaires will be used to measure mood in primary caregivers; - Global Health Questionnaire (GHQ) 12 This will be completed at baseline, 12 & 24 weeks following randomisation and subsequently at 24 week post patient mortality. | Baseline, 12 & 24 weeks & 24 weeks post mortality of the patient. | 
| Overall Survival between the two study groups | Overall survival from date of randomisation will be compared. Patients alive at the End of the Study will be recorded as 'alive' to ensure there is no missing data. | From randomisation to death or end of study (whichever occurs first), assessed up to 38 months | 
| Healthcare Utilisation between the two study groups | Healthcare resource use will be obtained from hospital, hospice and primary care databases after patient death or End of Study. | up to 24 weeks post patients death | 
| Primary caregiver satisfaction with end of life care | Primary caregiver satisfaction with end of life care as assessed by the Family Caregive Survey 2 (FAMCARE-2) questionnaire at 12 & 24 weeks and 24 weeks post mortality of the patient. | 12 & 24 weeks and 24 weeks post mortality | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelioma, Specialist Palliative Care, Symptom Control, Early Referral, Quality of Life, Malignant Pleural Mesothelioma