Evidence map›Paper›PMID 24743706›Full record

Trial reportBritish journal of cancer2014

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

T S Maughan, A M Meade, R A Adams, S D Richman, R Butler, D Fisher, R H Wilson, B Jasani, G R Taylor, G T Williams and 15 more

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

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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

25 authors at 9 institutions in 1 country.

T S MaughanCRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK.
A M MeadeMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
R A AdamsCardiff University and Velindre Cancer Centre, Cardiff, UK.
S D RichmanLeeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
R ButlerUniversity Hospital of Wales, Cardiff CF14 4XW, UK.
D FisherMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
R H WilsonCentre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7AE, UK.
B JasaniInstitute of Cancer and Genetics, Cardiff University, Cardiff CF14 4XN, UK.
G R TaylorLeeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
G T WilliamsInstitute of Cancer and Genetics, Cardiff University, Cardiff CF14 4XN, UK.
J R SampsonInstitute of Cancer and Genetics, Cardiff University, Cardiff CF14 4XN, UK.
M T SeymourSt James's Institute of Oncology, University of Leeds, Leeds LS9 7TF, UK.
L L NicholsMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
S L KennyMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
A NelsonWales Cancer Trials Unit, Cardiff University, Cardiff CF14 4YS, UK.
C M SampsonWales Cancer Trials Unit, Cardiff University, Cardiff CF14 4YS, UK.
E HodgkinsonSheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, UK.
J A BridgewaterUCL Cancer Institute, London WC1E 6BT, UK.
D L FurnissSheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, UK.
R RoyDepartment of Oncology, Castle Hill Hospital, East Riding of Yorkshire HU16 5JQ, UK.
M J PopeMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
J K PopeMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
M ParmarMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
P QuirkeLeeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
R KaplanMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London WC2B 6NH, UK.
Cardiff University · GBUniversity of Leeds · GBSheffield Teaching Hospitals NHS Foundation Trust · GBCardiff Metropolitan University · GBCastle Hill Hospital · GBCRUK Lung Cancer Centre of Excellence · GBCRUK/MRC Oxford Institute for Radiation Oncology · GBQueen's University Belfast · GBUniversity Hospital of Wales · GB

Funding

Cancer Research UK 15954Cancer Research UK 18815Marie Curie MCCC-FCO-11-CMedical Research Council G0701770Medical Research Council MC_U122861325Medical Research Council MC_UU_12023/3
6 · The paper itself

Abstract

backgroundMolecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. PATIENTS AND

methodsPatients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.

resultsA total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.

conclusionsPatient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Indexed as

Precision MedicineAgedAged, 80 and overBiomarkers, TumorColorectal NeoplasmsDisease-Free SurvivalDNA Mutational AnalysisFeasibility StudiesFemaleHumansMaleMiddle AgedProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsBiomarkers, TumorBRAF protein, humanKRAS protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID24743706
PMCPMC4007241
OpenAlexW2055159351

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.