Title: CANCER: Trials with potential global reach and other challenging trials
Funder: Medical Research Council

Abstract: This theme relates to trials that either present unusual challenges to design and conduct and/or have the potential for global impact (that is, studies of specific relevance to both resource-poor and resource-rich countries). Challenging trials include those that draw upon this Unit’s specialised experience, such as those requiring extremely large recruitment numbers and/or practical experience managing international collaboration. One class of trials with global reach involves tests of ‘repurposing’ an approved and marketed drug in an indication distinct from that for which it was licensed. There is currently considerable interest in re-evaluating commonly prescribed medications for their anti-cancer properties. Repurposing studies have significant potential benefits. Demonstrating efficacy in a new clinical indication for drugs with known toxicity and pharmacokinetics bypasses or shortens some of the steps of the traditional drug evaluation pathway. It also provides access to drugs that are often relatively simple to administer and considerably less expensive than newer agents still within their patent life, and therefore of particular benefit in resource-limited settings. The assessment of aspirin as an adjuvant therapy in several different cancer types within the Add-Aspirin programme is a classic example of such repurposing, as is the ongoing PATCH trial which is evaluating oestradiol patches, designed originally for use in post-menopausal women, as a treatment for prostate cancer. Systematic review is a key tool for deciding which agents are the best candidates for further evaluation; statins, vitamin D and metformin (an oral hypoglycaemic agent used to treat diabetes), amongst others, are currently being actively investigated for inclusion in either the STAMPEDE and/or the Add-Aspirin trial platforms. In low resource countries, approximately one quarter of all cancers have been attributed to four chronic infectious causes: helicobacter pylori, hepatitis B and C, and human papilloma virus (HPV). HPV-associated tumours develop mainly in the ano-genital area and oropharynx and all have similar molecular signatures and clinical characteristics. We are actively exploring the feasibility of new platform trials that will bring together researchers with a common interest in HPV-related (or other infection-related) cancers. HPV cancers all contain foreign HPV antigens, which provides an opportunity to exploit immunological based therapies and strategies that have recently led to improved outcomes in other tumour types. Some cancer trials fit into our portfolio because of particular challenges and their potential impact. Amongst these is the PROMIS study which is testing, in patients with suspected prostate cancer, a diagnostic pathway that includes Multi-Parametric Magnetic Resonance Imaging (MP-MRI). Whilst this is a UK-only study, it is in an extremely common disease setting and has the potential to reduce the substantial over-diagnosis and overtreatment of low grade prostate cancers that carry little risk to survival – a common problem across Western countries. Improving the diagnostic accuracy for prostate cancer, the most common neoplasm in men, would have a huge impact on resource usage, outcomes, and quality of life. Perhaps most importantly, it could provide the basis for a sound approach to prostate cancer screening which has thus far proved a challenge to public health authorities internationally.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS