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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?
- Source :
- British Journal of Cancer, Maughan, T S, Meade, A M, Adams, R A, Richman, S D, Butler, R, Fisher, D, Wilson, R H, Jasani, B, Taylor, G R, Williams, G T, Sampson, J R, Seymour, M T, Nichols, L L, Kenny, S L, Nelson, A, Sampson, C M, Hodgkinson, E, Bridgewater, J A, Furniss, D L, Roy, R, Pope, M J, Pope, J K, Parmar, M, Quirke, P & Kaplan, R 2014, ' 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? ', British Journal of Cancer, vol. 110, no. 9, pp. 2178-2186 . https://doi.org/10.1038/bjc.2014.182
- Publication Year :
- 2014
- Publisher :
- Springer Nature, 2014.
-
Abstract
- Background:\ud \ud Molecular 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.\ud \ud \ud Patients and Methods:\ud \ud Patients 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.\ud \ud \ud Results:\ud \ud A 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.\ud \ud \ud Conclusions:\ud \ud Patient 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.
- Subjects :
- Male
Proto-Oncogene Proteins B-raf
Cancer Research
medicine.medical_specialty
DNA Mutational Analysis
colorectal cancer
medicine.disease_cause
Disease-Free Survival
law.invention
Proto-Oncogene Proteins p21(ras)
RC0254
SDG 3 - Good Health and Well-being
Randomized controlled trial
law
Proto-Oncogene Proteins
Internal medicine
Biomarkers, Tumor
medicine
Humans
Precision Medicine
Aged
Aged, 80 and over
Cetuximab
business.industry
multi-arm trials
personalised medicine
biomarkers
Combination chemotherapy
Middle Aged
Surgery
Irinotecan
Clinical trial
Treatment Outcome
Oncology
Cohort
Clinical Study
ras Proteins
FOLFIRI
Feasibility Studies
Female
KRAS
Colorectal Neoplasms
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer, Maughan, T S, Meade, A M, Adams, R A, Richman, S D, Butler, R, Fisher, D, Wilson, R H, Jasani, B, Taylor, G R, Williams, G T, Sampson, J R, Seymour, M T, Nichols, L L, Kenny, S L, Nelson, A, Sampson, C M, Hodgkinson, E, Bridgewater, J A, Furniss, D L, Roy, R, Pope, M J, Pope, J K, Parmar, M, Quirke, P & Kaplan, R 2014, ' 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? ', British Journal of Cancer, vol. 110, no. 9, pp. 2178-2186 . https://doi.org/10.1038/bjc.2014.182
- Accession number :
- edsair.doi.dedup.....cff73b2cbc37e2e73c551850137aa559