Mark Middleton’s research concentrates on development of new cancer drugs and on the treatment of melanoma.
Early phase clinical trials
Our aim is to bring the excellent science in Oxford to cancer patients. Our strategy is to develop new treatments or combinations of treatments through the concepts of ‘synthetic lethality’ and oncogenic vulnerability. To deliver this we have established the infrastructure to perform detailed analyses of tumours before, during and after intervention to select patients; to test our a priori hypotheses; and to better understand the biological effects of treatment.
We look to deliver smaller trials involving subsets of patients. These have the ability to change patient care, by focussing our efforts on tightly defined clinical populations to maximise differences in outcome, moving away from one-size-fits-all phase 3 trials with purely correlative translational studies. Through the Oncology Clinical Trials Office (OCTO; setting up studies to run in centres all around Europe) and the Early Phase Clinical Trials Unit (EPCTU; running trials in the Oxford Cancer and Haematology Centre) we have established one of the largest academic early phase trials portfolios in Europe.
Recently we have seen incredible advances in the treatment of advanced melanoma. The challenges now are to understand why not all patients benefit from the new drugs at our disposal. Genetic characteristics or signatures are being explored to identify patients who are likely to benefit from particular treatments and to make informed treatment decisions on the best combinations of drugs to use in the clinic.
For example, we have defined new combinations of radiotherapy with vandetanib and of paclitaxel with trametinib, and are active in the development of new drugs such as IMCgp100, MLN2480, T-Vec and IMM47. We are looking into biological markers to identify patients most likely to benefit from bevacizumab therapy in the national AVAST-M study, starting with those whose melanoma has a mutation in the BRAF gene.
Mark Middleton is Professor of Experimental Cancer Medicine in the Department of Oncology, consultant Medical Oncologist at the Oxford Cancer and Haematology Centre and Head of the Department of Oncology at the University of Oxford (from April 2017). Mark is the Lead Cancer Clinician for the Oxford University Hospitals NHS Foundation Trust and Director of the Cancer Research UK Oxford Centre. He directs the EPCTU and the Cancer Theme of the NIHR Biomedical Research Centre. He studied medicine at Cambridge and Oxford and trained in medical oncology at the Christie Hospital. Mark is a member of the International Melanoma Working Group and of the NCRI Melanoma Clinical Studies Group. He leads several clinical trials in the national portfolio
PACMEL: A phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel (2014). Coupe N, Corrie P, Hategan M, Larkin J, Gore M, Gupta A, Wise A, Suter S, Ciria C, Love S, Collins L, Middleton MR. Eur J Cancer. [Epub ahead of print] PubMed PMID: 25542057.
DOC-MEK: A double blind randomized phase 2 trial of docetaxel with or without selumetinib in wild-type BRAF advanced melanoma (2014). A. Gupta; S. Love; A. Schuh; M. Shanyinde; J. M. Larkin; R. Plummer; P. D. Nathan; S. Danson; C. H. Ottensmeier; P. Lorigan; L. Collins; A. Wise; R. Asher; R. Lisle; M. R. Middleton. Ann Oncol ; doi: 10.1093/annonc/mdu054
Phase II Pilot Study of Intravenous High-Dose Interferon With or Without Maintenance Treatment in Melanoma at High Risk of Recurrence (2014). Payne MJ, Argyropoulou K, Lorigan P, McAleer JJ, Farrugia D, Davidson N, et al. J Clin Oncol. 32:185-190.