We continue to build and expand Investigator led studies and there are now eight Barts-led, investigator-initiated, grant-funded early phase clinical trials either open or in set-up: DB4, Diffusion-PET, MARALL, REGiME, CO328X05, ADAM, CarPET and SelRICE. These trials are all driven by the research interests of the Chief Investigators and are funded either wholly or in part by research grants from organisations including MRC, CR-UK and the Leukaemia Research Fund. ADAM is an excellent example of true translational research: the pre-clinical laboratory data underpinning the trial have been generated by Dr Peter Szlosarek as part of his CR-UK Clinician Scientist Fellowship and the trial funding is provided by a separate CTAAC grant, with collaboration from Polaris Pharmaceuticals. In addition, there are several commercially-funded investigator-initiated studies with Barts Chief Investigators. These include SuMR (Sunitinib in metastatic renal cancer, funded by Pfizer) and Panther (Pazopanib in renal cancer, funded by GSK). Finally, SaPPROC, one of the trials that has emerged from the Astra-Zeneca/NCRN collaboration and is funded by the CTAAC Feasibility Committee, has a Barts Chief Investigator. These trials will all benefit patients by allowing them to access to novel agents, assessed using novel imaging techniques. Without the trials infrastructure that is supported by ECMC funding, it would be impossible to run all of these studies. A key component of all these studies is the close working relationship between the clinical investigators in the ECMC and the scientists within the CRUK Clinical Centre to maximise the translational components of these studies.

Barts was selected as one of only 8 designated Myeloma UK clinical trial network centres. This centre will be embedded within the ECMC and led by Dr Jamie Cavenagh. Through this funding, a new research nurse, post-doctoral research fellow and data manager will be employed to strengthen our already impressive portfolio of early phase clinical trials in multiple myeloma. This will benefit patients by broadening the range of novel agents to which they have access. Other evidence of national leadership comes from the 31 national trials in which the Chief Investigator is based at Barts. Barts investigators are members of the Breast, Leukemia, Lymphoma, CLL, Gynaecology and Correlative Science CSGs. John Gribben and Chris Gallagher both sit on CTAAC, Iain McNeish is a member of the CTAAC advisory panel and CR-UK Central Institutional Review Board. Internationally, John Gribben is a Principal Investigator in the CLL Consortium, Tom Powles is a member of the EORTC urological cancer group and Iain McNeish is a member of the Gynecologic Cancer Intergroup.

Following the successful MHRA inspections at the end of 2008, where no critical findings were found following inspection of both Barts and the London Trust and the School of Medicine and Dentistry, several ECMC trials have undergone successful audit from the Trust and Medical School Joint Research Office during 2009. In addition, in conjunction with the Trust Cancer clinical academic unit (CAU), the ECMC has established a new governance structure. The Research Governance committee examines all potential trials prior to set-up and also all clinical trials applications prior to external peer review, to ensure that they are scientifically valid and will satisfy the tenets of Good Clinical Practice. In addition, all trials are formally reviewed 12 months after local approval to ensure that they are meeting their recruitment targets and remain relevant to the overall trial portfolio. We have been working with CRUK and Professor Peter Sasieni in the Cancer Prevention CTU and to move the operation of these ECMC studies into the CTU and work closely with the CTU to improve further QA and governance of the clinical trial portfolio.

There are currently 106 cancer clinical trials open and recruiting at Barts, a significant increase since the start of ECMC funding in 2007. During the last 6 months of 2009, recruitment to all trials has averaged over 60 patients per month.

We continue to open studies in areas of unmet clinical need and which lie outside the tumour types that have traditionally been very strong at Barts (haematological and urological malignacies). In addition to pancreatic and ovarian cancers that were reported previously, early phase trials are now open in mesothelioma, melanoma, upper GI malignancies, endometrial and cervical cancers. One of the new trials, DEPICT, is a study of intensity-modulated radiotherapy, a modality under-represented in UK clinical trials.

The establishment of the ECMC has enabled new investigators, especially those involved in breast, colorectal and gynaecological cancers, to develop the infrastructure required for sustained trials recruitment. In ovarian cancer, for example, 29% patients referred to Barts for treatment since January 2007 have been recruited clinical trials, with the majority entering phase II trials and Barts is the top recruiting site for AML17. A key component of our studies remains the banking of tumour samples for biomarker analysis.

Imaging remains a core strength of the Barts ECMC. In 2009, several pure imaging studies have been initiated. These include demobesin-4, which is a New Agents’ Committee-funded trial of PET imaging in newly diagnosed advanced prostate cancer and Ovarian FDG-PET, one of the first trials to investigate the power of FDG-PET response marker across two centres. Professor Andrea Rockall will initiate Diffusion-PET early in 2010, to investigate the ability of DW-MRI and FDG-PET to identify lymph node metastases in gynaecological cancers, whilst Dr Sylvia Montoto will lead a study comparing FDG and FLT-PET in relapsed diffuse large B cell NHL, funded by a $300,000 grant from Genentech.

Through the NIHR Capital Equipment call, the Barts ECMC was awarded £468,000 to purchase two mass spectrometry systems. These are now operational and are being used by Dr. Simon Joel and his group within the ECMC for high throughput pharmacokinetics and metabolite measurement. This equips the centre to perform high value PK analyses in early phase clinical trials. They will also be used to quantify proteins, phosphoproteins, metabolites and enzymatic activities as biomarkers of drug response.