Dr Anna Bibby Post CCT NIHR Research Fellow - PowerPoint Presentation

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Dr Anna Bibby

Post CCT NIHR Research FellowUniversity of Bristol & North Bristol NHS Trust

An update on clinical trials in mesothelioma

For the SWAG Network Lung SSG Meeting, 22/05/18

Overview

Summary of trials currently recruiting at NBTTARGETASSESS-mesoTILTMARS2Meso-TRAPEligibilityTrial processesHow to get your patient involved

Randomised controlled trial to compare the diagnostic yield of Positron Emission Tomography Computed Tomography (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy.

Multicentre randomised trialPET vs CT-guided biopsyNIHR RfPB funded1 o/c - diagnostic accuracy2 o/c - Time to diagnosis- Number of procedures- Healthcare costsN = 45/78Closes 30/9/18

EXCLUSION CRITERIAUnsuitable for a CT guided biopsy Inability to co-operate/lie stillUncorrectable coagulopathyInability to tolerate PTxSevere underlying lung disease (FEV1 < 35%)Pleural thickening not amenable to a radiologically guided biopsyTalc pleurodesis in past 6 moINCLUSION CRITERIAPleural thickening on CT, suspicious for pleural malignancyPrevious non-diagnostic pleural biopsy in the past 12 monthsMDT decision to perform further CT-guided biopsy to pursue a diagnosis

A prospective obServational cohort Study collecting data on dEmographics, Symptoms and biomarkerS in people with mesothelioma that will provide a resource for future trials

Multicentre pragmatic observational studyFunding: Avon Mesothelioma FoundationAll-comers with mesotheliomaFollowed up from diagnosis to deathAims:To explore natural history of diseaseTo describe symptoms & symptom evolutionTo investigate factors affecting outcomesTo provide a resource for biomarker testingN = 23/700

EXCLUSION CRITERIAAge <18 years oldUnable to give written informed consentDeclines ongoing hospital follow upINCLUSION CRITERIAHistological, cytological or clinico-pathological diagnosis of MPM, confirmed at MDTWilling & able to comply with study follow up assessments (including at least 1 appointment at a study centre)Able to provide written informed consent

Meets eligibility criteria

Study assessments

alongside clinic

appts

Option to switch to telephone/ postal F/U

Able/

willing to continue clinic

F/U?

YES

NO

Minimum every 3 months

Clinical assessment, imaging, blood tests, fluid assessment, PROMS

Clinical history

inc

drainage

vols

, PROMS, recent bloods/ imaging if appropriate

Death or withdrawal from study

A

T

rial of

I

ntra-

pleura

L

bacterial immuno-

T

herapy in mesothelioma:

A feasibility study using the ‘trial within a cohort’ methodology

Randomised 3-arm feasibility trialBased on “trials within cohorts” designIntra-pleural OK432 vs BCG vs usual careFunded by NIHR DRF Primary outcome – feasibilitySecondary outcomes – response rates, survival, PROMSN=1/24 Further 12 months recruitment

EXCLUSION CRITERIAContra-indication to IPC Trapped lung or heavily loculated effusionKnown immunodeficiency or immuno-suppressive medicationIntercurrent infection Known allergy to OK432, BCG or penicillinPrevious immunotherapy Brain metastases or CNS involvementINCLUSION CRITERIAPathological diagnosis of MPM & enrolled in ASSESS-mesoFunctioning IPC in situ or willing (& able) to have one inserted No chemotherapy planned for 4 weeks either side of trialPerformance status ≤3Predicted survival ≥12 weeks

Intra-pleural OK432

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

Potentially eligible patientEligibility confirmed by surgical team

ConsentRandomisation2 cycles of chemotherapy, then CTNo surgeryUp to 4 cycles of chemotherapy

(Extended) pleurectomy decortication

Follow up at 6 weeks, 6 months, 12 months, 18 months & 24 months

Bristol

Bristol

Bristol

Bristol

Locally

Locally

London

London, in absentia

INCLUSION CRITERIA≥16 years oldTissue confirmed mesothelioma Disease confined to one hemi-thorax on CTDisease deemed surgically resectable Fit for surgery Able to provide written informed consentEXCLUSION CRITERIASevere shortness of breath PS ≥ 2Pre-operative FEV1 or TLco <20% Serious concomitant disorder that would preclude surgery Severe heart failure (EF <30%)

End stage kidney failure on dialysis Liver failurePrisoner Lacks capacity to consent Enrolled in another interventional trial

Meso-TRAPA study comparing video-assisted thoracoscopic partial pleurectomy/decortication (VATS-PP) with indwelling pleural catheter (IPC) in patients with trapped lung due to malignant pleural mesotheliomaRandomised feasibility studyPatients have to have “clinically significant trapped lung requiring intervention”Must be fit enough & willing to undergo VATS-PPN=4/38

How do I get my patient into a trial?All patients discussed at NBT Mesothelioma MDT are screened for eligibilityAll patients seen in NBT pleural/meso clinic are screenedWe are happy to receive referrals asking re trial eligibilityAlso happy to discuss any potentially eligible patients over the phone

ConclusionMeso trials are available at (almost) every step of the patient pathwayTARGETASSESS-mesoTILTMARS2Meso-TRAPAll require the patient to travel to Bristol at least onceBut some treatments can be given locally to reduce travel burdenProf Maskell & I are always happy to discuss potential patients prior to referralDiagnosticObservationalImmunotherapy

Surgery

Thank you very much Any questions?Anna.Bibby@nbt.nhs.uk Nick.Maskell@bristol.ac.ukTel: 0117 414 8049 Mob: 07724912367