Sheffield ECMC has made novel treatments available to patients in South Yorkshire through participation in early phase clinical trials of chemotherapy, biologically targeted agents, radioisotopes, radiotherapy and novel imaging modalities. This has been achieved through participation in phase I/II trials available through CRUK, collaborative groups (e.g. EORTC, NCRI) and partnership with pharma (e.g. AstraZeneca, GSK, Immunogen, Novartis, Pfizer, Sanofi-Aventis).

Sheffield ECMC is active in developing clinical trials of new agents and related laboratory studies, particularly in breast cancer, lung cancer and soft tissue sarcomas.

• ARIAD study of musculoskeletal adverse effects of aromatase inhibitors
  This study has been evaluating the effects of aromatase inhibitors on joint function and grip strength, using multiple imaging techniques (ultrasound, MRI and DEXA) and blood biomarkers (type II collagen markers and rheumatological indices) in breast cancer patients receiving tamoxifen or aromatase inhibitors. This study will determine whether imaging or blood biomarkers can identify patients at risk of musculskeletal adverse effects of aromatase inhibitors.
• ANZAC study of antitumour effects of bisphosphonates
  This proof of principle study is testing whether the preclinically identified sequence-dependent synergy between zoledronic acid and anthracyclines in breast cancer translates into clinical practice. Tumour biopsies are taken before and after neoadjuvant chemotherapy with or without zoledronic acid. Samples are assessed for apoptosis, proliferation, angiogenesis and circulating tumour cells. Recruitment has been completed on time.
• Clinical and translational studies of axitinib in sarcoma
  We have set up a multicentre, NCRI approved, phase II study of axitinib in angiosarcoma and other sarcomas. This will test the safety and efficacy of oral axitinib in patients with advanced disease. In parallel with this, a clinical research fellow (funded by Yorkshire Cancer Research) is undertaking detailed mechanistic studies in the laboratory.

We continue to recruit patients and bank samples in a wide range of genetic epidemiology studies in melanoma, breast, lung and prostate cancer. These projects are now proceeding to analyse the samples:

• AZURE biomarker study
  Over 3000 patients have been recruited to this phase III trial of adjuvant zoledronic acid in patients with high risk localised breast cancer. We have been biobanking their clinical samples and have now obtained funding and NIHR approval for the correlative bone biomarker study evaluating bone mineral density, blood and urine biomarkers and novel quantitative bone scanning techniques. This study will help determine whether biomarkers can identify patients who will benefit from adjuvant bisphosphonates.
• Plasma DNA for genetic studies in lung cancer patients and controls
  We have optimised a method for the efficient extraction of DNA from plasma and demonstrated that the products can be used for mutation screening. Preliminary analyses have used samples from the ReSoLuCENT study. Quantifiable DNA was obtained from 99% of plasma samples. Plasma DNA levels were significantly higher in lung cancer patients than controls. DNA was amplified using a whole genome amplification technique and mutations were detected by PCR-SSCP and sequencing.

With the aid of DH funding, the Sheffield ECMC installed a 9.4T microimaging and spectroscopy system in July 2009 to investigate clinical samples. Several acquisition modes are available including high resolution multi-nuclear spectroscopy, high resolution multi-nuclear micro imaging and high resolution ‘Magic Angle Spinning’. All modes have now been tested and the system is operating very effectively. The samples we have already examined include:

• We are analysing drug concentrations in clinical samples, including zoledronic acid and combretastatin CA-1-P and CA-4-P vascular targeting agents. We have already shown it is possible to hyper-polarise CA-4-P and eventually after enrichment we will investigate the in vivo bio-distribution. This will be invaluable for pharmacokinetic studies.
• High quality spectral data has been collected from archived plasma and urine samples from breast cancer patients. Spectral assignment is in process.