Evidence map›Paper›PMID 26410619›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2015

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer.

G Middleton, L R Crack, S Popat, C Swanton, S J Hollingsworth, R Buller, I Walker, T H Carr, D Wherton, L J Billingham

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02664935 (National Lung Matrix Trial), which is not on this map. Cited by 34 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 3 pooled it
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02664935 phase2completednot on this map

National Lung Matrix Trial: Multi-drug, Genetic Marker-directed, Non-comparative, Multi-centre, Multi-arm Phase II Trial in Non-small Cell Lung Cancer

TypeinterventionalSponsorUniversity of BirminghamRan2015 to 2023Enrolled423ConditionsNon-Small Cell Lung Cancer, Carcinoma, Squamous Cell, AdenocarcinomaArmsAZD4547, Vistusertib, Palbociclib, Crizotinib, Selumetinib
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  15. Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Prior Therapies Work Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  16. Review
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  19. Review
  20. Biomarker-guided trials: Challenges in practice.Contemporary clinical trials communications · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 8 institutions in 4 countries.

G MiddletonInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham Department of Oncology, University Hospitals Birmingham NHS Foundation Trust, Birmingham g.middleton@bham.ac.uk.
L R CrackCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham.
S PopatDepartment of Medicine, Royal Marsden NHS Foundation Trust, London.
C SwantonThe Francis Crick Institute, London UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, London.
S J HollingsworthInnovative Medicines Oncology, AstraZeneca, Cambridge, UK.
R BullerPfizer Oncology, Pfizer, San Diego, USA.
I WalkerStrategy and Research Funding, Cancer Research UK, London, UK.
T H CarrInnovative Medicines Oncology, AstraZeneca, Cambridge, UK.
D WhertonCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham.
L J BillinghamCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham.
AstraZeneca (United Kingdom) · GBUniversity of Birmingham · GBCancer Research UK · GBCancer Research UK Clinical Trials Unit · GBCRUK Lung Cancer Centre of Excellence · GBPfizer (United States) · USRoyal Marsden NHS Foundation Trust · GBUniversity Hospitals Birmingham NHS Foundation Trust · GB

Funding

Cancer Research UK 17786Cancer Research UK 18632Cancer Research UK 19310Cancer Research UK 19363Cancer Research UK 20605Cancer Research UK C11497/A19363Cancer Research UK C22436/A18392
6 · The paper itself

Abstract

backgroundThe management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. PATIENTS AND

methodsThe Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse.

conclusionThe SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC. CLINICAL TRIAL ISRCTN: 38344105.

Indexed as

Antineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsNeoplasm Recurrence, LocalProto-Oncogene Proteins c-aktPyrimidinesPyrrolesTranslational Research, BiomedicalUnited KingdomAntineoplastic AgentsBiomarkers, TumorcapivasertibProto-Oncogene Proteins c-aktPyrimidinesPyrrolesadaptive trial designNational Lung Matrix Trialnon-small-cell lung cancerstratified medicineUmbrella Trial

Identifiers

PMID26410619
PMCPMC4658545
OpenAlexW2179283632

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.