Funding from ECMC has been used to leverage funding from NIHR to the Cambridge Biomedical Research Centre and CRUK to create the Cambridge Early Phase Clinical Trials Team (EPCTT), and together with Merck to provide Cambridge with PET-CT facilities. EPCTT is conducting all the early phase trials in Cambridge and the number of patients enrolled has tripled in 3 years (from 7 in 2007 to 23 in 2009):

• 38 patients were screened and 23 entered into early phase trials
• Seven new studies have been initiated in 2009

Importantly now the EPCTT is in place Cambridge can apply to CR-UK NAC and run DDO studies, as is already happening with Dave Tuveson's trial of a Notch inhibitor in advanced pancreatic cancer. EPCTT is also going to conduct CTAAC Feasibility studies with Tim Eisen (in bronchial pre-neoplasia) and Colin Watt (in glioma).

Now the EPCTT infrastructure, together with PK/PD laboratories at CRI, is in place Cambridge becomes competitive to attract Pharma (after all the providers of most of the new compounds) so they do trials here. This is already happening with Merck, GSK, AZ, and Pfizer. The interaction with Merck goes even further since Cambridge becomes one of only two UK centres that will be part of the Onconet network. This not only brings substantial core funds to strengthen the existing ECMC, NIHR BRC and CRUK Cancer Centre infrastructure, but it also means a minimum of 50 new patients enrolled in early phase trials every year.

To use cancer drugs better means to deliver them such that the patient gets the benefit (cancer cure or cancer control) with minimal toxicity- the ultimate goal of personalized cancer medicine. This is one of the main aims of the Cambridge ECMC. In order to achieve this goal clinical trials have to be conducted such that not only the clinical effect of the drug is tested (measured as either improved survival or tumour shrinkage), but biomarkers that could be used as surrogates of clinical benefit are also prospectively analysed. This requires usually intensive imaging (ECMC-funded 3T MRI, Pet-CT) and repeated biopsies (ECMC/NIHR-funded endoscopy suites for UGI, pancreas and lung), frequently in the neoadjuvant setting and our Centre has developed the expertise and infrastructure to do these translational trials.

One of the areas of expertise in Cambridge is the conduct of neoadjuvant translational clinical trials to identify molecular and imaging biomarkers that predict response to currently available treatments.

During 2009 this activity continued to expand significantly:

• Breast cancer neoadjuvant therapy studies actively enrolling patients (MONET, Neo- Persephone, ARTEMIS, ARTIST)
• Circulating tumour cells in metastatic breast cancer patients continued (DETECT)
• Ovarian cancer neoadjuvant chemotherapy study completed (CTCR-OV03)
• Prostate cancer study for predicting androgen resistance in the clinic started

The ECMC-funded 3T MRI facility has had significant activity over the past 12 months with 130 study scans done in 71 patients and a further 54 method-development scans done in volunteers. The following studies have been enrolling patients or have finished recruitment in the past 12 months:

1. Profiling signatures of chemotherapy response in ovarian cancer: Correlation with functional MRI.
2. The role of functional MRI in predicting tumour response to androgen deprivation in advanced prostate cancer.
3. Predicting Response of Non-Hodgkin’s Lymphoma to Chemotherapy. This is part of a multicentre trial funded by the NCI (Multi-Institutional Trial R01 CA118559-01A1/ Brown) looking at whether response of NHL to chemotherapy can be predicted from a pre-treatment measurement of tumour phosphomonoesters and cholines using MRS.
4. Serial evaluation of patients with hepatocellular carcinoma and cirrhosis with BOLD, DWI, MRE, and DCE–MRI using 3T MRI. This project aims to establish whether there is a significant difference between the responses of HCC, cirrhotic liver and normal liver to increased inspired oxygen levels as measured by the BOLD effect.
5. Brain 1H MRS: Repeatability of tumour lactate measurements. This is a collaborative project with Merck & Co. and is a first step towards potential future projects using lactate as a biomarker in drug intervention studies involving tumours in the brain and other locations.
6. The role of advanced brain MRI techniques in small cell lung cancer. This project aims to improve the management of patients with small cell lung cancer by developing methods for early detection and prediction of spread to the brain.
7. A feasibility study to assess liver and breast tumour tissue using 19F MRS. This study aims to develop methods for quantification of capecitabine and its metabolites in breast tumours and in the liver. Relationships between 19F metabolite levels and response will be explored.
8. Evaluation of MRS and DWI MRI in the diagnosis of follicular thyroid nodules and parotid lumps. This project aims to investigate the application of MRS and DWI to diagnose follicular thyroid lesion and parotid lumps preoperatively. Brain 1H MRS: Repeatability of tumour lactate measurements. This is a collaborative project with Merck & Co. and is a first step towards potential future projects using lactate as a biomarker in drug intervention studies involving tumours in the brain and other locations.

We have also started significant activity in PET-CT. For example, we lead (Brenton, chief investigator) an NCRI-approved PET/CT multi-centre study evaluating FDG as a marker of response in patients with relapsed ovarian cancer receiving platinum-based chemotherapy (Merck 000 P143). This is the first study examining FDG-PET as a biomarker of resistance in relapsed disease and the study has recruited to date 8 patients from the two participating sites.

Cambridge has particular expertise in ‘clinical genomics’ requiring development of integrated databases:

• Developed a metadata approach to integrate clinical data with SNP- and expression array data
  
  

CECMC has continued its activity aimed at developing biomarkers and strategies for the management of pre- and early neoplasia in high risk groups:

Markers of progression in Barrett's-adenocarcinoma identified:

• Capsule sponge for non-endoscopic screening biomarkers for Barrett’s oesophagus now being tested prospectively
• Early gastric cancer in E-cadherin mutation carriers.
• Identification, monitoring and treatment of pre-malignant bronchial epithelial dysplasia