DIAPHRAGM: Diagnostic and prognostic biomarkers in the rational assessment of mesothelioma

• Register: ISRCTN
• Last refreshed on: 20 November 2017
• Main ID: ISRCTN10079972
• Date of registration: 17/10/2013
• Prospective Registration: Yes
• Primary sponsor: NHS Greater Glasgow and Clyde (UK)
• Public title: DIAPHRAGM: Diagnostic and prognostic biomarkers in the rational assessment of mesothelioma
• Scientific title: DIAPHRAGM study: to prospectively assess whether the levels of two novel biomarkers (SOMAscan and Fibulin-3) in blood, can distinguish between malignant pleural mesothelioma (MPM), other malignant pleural effusions and from people who have had previous exposure to asbestos but have no evidence of MPM
• Date of first enrolment: 01/11/2013
• Target sample size: 709
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN10079972
• Study type: Observational
• Study design: Prospective multi-centre observational study incorporating a nested cross-sectional sub-study (Diagnostic)
• Phase: Not Applicable

Countries of recruitment

Ireland, United Kingdom

Contacts

• Name: Kevin Blyth

Key inclusion & exclusion criteria

Inclusion criteria: Cases of suspected pleural malignancy:
1. Informed written consent
2. Suspected pleural malignancy, as defined by a unilateral pleural effusion or pleural-based mass lesion
3. Sufficient fitness for diagnostic sampling, including diagnostic pleural aspiration as a minimum
4. Aged over 18

Patients with suspected pleural malignancy recruited to the cross-sectional sub-study will be subject to the following additional inclusion criteria:
1. Recruited in a WoS centre (Southern General, Gartnavel General, Glasgow Royal)
2. Thoracoscopy indicated to investigate suspected pleural malignancy (defined by negative pleural cytology and non-specific CT findings)
3. Aged over 18

Asbestos-exposed subjects:
1. Documented history of asbestos exposure and associated pleural plaques, asbestosis or diffuse pleural thickening
2. Informed written consent
3. Willing and able to travel to a research clinic interview in Glasgow
4. Aged over 18
Exclusion criteria: Cases of suspected pleural malignancy:
1. Insufficient fitness (based on the site investigator?s clinical judgement) for diagnostic sampling, including diagnostic pleural aspiration as a minimum

Patients with suspected Pleural Malignancy recruited to the cross-sectional sub-study will be subject to the following additional exclusion criteria:
1. Claustrophobia
2. Pregnancy
3. Unable to undergo MR imaging due to known contraindications (e.g. pacemaker, ferrous metal implants or foreign body)
4. Allergy to Gadolinium contrast
5. Renal impairment (eGFR <30ml/min)

Asbestos-exposed subjects:
1. Known MPM
2. Known pleural effusion of any cause

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Suspected pleural malignancy or documented history of asbestos exposure
Cancer

Intervention(s)

Patients with suspected pleural malignancy:
Visit 1 (Day 0, first clinic visit or in patient stay at hospital)
Core Study Activity:
1. Asbestos exposure history
2. Review eligibility criteria
3. Introduce to study if eligibility criteria met
4. Provide with Core Study Patient Information Sheet (at clinic or via post)

Visit 2 (Day 3)
Core Study Activity:
1. Opportunity for discussion regarding study
2. Sign core study consent form
3. Register patient with Clinical Trials Unit
4. ECOG Performance Status
5. Blood draw for biomarkers with appropriate processing and storage
6. Asbestos exposure history (if not previously performed)
7. Record baseline prognostic indicators, including haemoglobin, leucocyte and platelet counts, lactate dehydrogenase, c-reactive protein and albumin

Visit 3 (Day 9)
Core Study Activity:
1. If a diagnosis of MPM is made - enter follow-up
2. If any non-MPM diagnosis made - exit study

MRI sub-study activity
If no diagnosis is made - consider MRI sub-study (only in WOS patients)
1. Review sub-study eligibility criteria
2. Introduce sub-study if eligible
3. Provide with separate sub-study PIS
4. MRI Safety Questionnaire
5. X-ray orbits if any history of eye injury and retained metallic foreign body

Visit 3a (Day 11-18)

Core Study Activity: None

MRI sub-study activity
1. Opportunity for further discussion with CRF
2. MRI Safety Questionnaire (if not previously recorded)
3. Sign sub-study Consent From
4. Register subject with CTU
5. Pleural MRI scan

Visit 4 (Day 14-21)

Core Study Activity:
No activity

MRI sub-study activity
Paired Blood and Pleural Fluid Draw for biomarkers with appropriate processing and storage

Visit 5 (day 23-31)
Core Study Activity:
1. If diagnosis of MPM made - enter follow-up
2. If non-MPM diagnosis made - exit study

MRI sub-study activity: None

Visit 6 (Day 62)
Core Study Activity:
Blood draw for SOMAscan and Fibulin-3

MRI sub-study activity: None

Visit 7 (Day 123)
Core Study Activity:
Blood draw for SOMAscan an

Primary Outcome(s)

1. SOMAscan and Fibulin-3 in blood at presentation
2. Final diagnosis reached

Secondary Outcome(s)

1. SOMAscan and Fibulin-3 levels at presentation and at 3 months
2. Survival

Exploratory Research Outcomes
1. Correlation between SOMAscan and/or Fibulin-3 levels and tumour volume, defined by planimetry at contrast-enhanced Magnetic Resonance Imaging
2. Correlation between SOMAscan and/or Fibulin-3 levels and tumour angiogenesis, Redistribution rate constant (Kep) and elimination rate constant (Kel)) on contrast-enhanced magnetic resonance (MR) imaging
3. SOMAscan and Fibulin-3 in paired blood and pleural fluid samples
4. SOMAscan and Fibulin-3 levels at presentation and at 1 month post-biopsy and pleurodesis

Secondary ID(s)

DIAPHRAGM-2013

Source(s) of Monetary Support

Chief Scientist Office (UK) Ref: ETM/285