The DETERMINE trial: showcasing Cancer Research UK’s unique position in the pharma industry

DETERMINE (Determining Extended Therapeutic indications for Existing drugs in Rare Molecularly-defined Indications using a National Evaluation platform) explores whether drugs targeting identifiable genomic alterations that are approved to treat some cancers could treat others, including rare types, in patients who have the same genetic alterations. Open to adults, teenagers and children, this is the UK’s first national precision medicine trial for rare cancers and will hopefully provide new treatment options for those who may not have any left. 

Through compassionate use requests pharmaceutical companies may provide drugs off-label and free of charge to patients where they believe there is a potential benefit. However, managing these requests is resource intensive, and outcome data are not routinely collected outside the scope of a clinical trial. DETERMINE offers a unique solution by allowing eligible patients to directly access these medicines in the context of a clinical trial. This approach not only streamlines access to potentially life-prolonging treatments but also enables the collection of valuable data to benefit many more patients in the future.  

Collaboration plays a crucial role in the success of a trial of this scale, and Cancer Research UK is vital in fostering this collaboration. With a vast network, including over 4,000 researchers and clinicians, the charity brings together a diverse range of expertise from across the country. A pivotal partner in this collaborative network is Cancer Research UK’s Centre for Drug Development, which sponsors and manages the DETERMINE trial. With its extensive experience of setting up novel, translation-driven early phase trials, it provides invaluable guidance and support to ensure the trial’s success.  

The collaborative network extends beyond Cancer Research UK through the involvement of other key individuals and institutions. The University of Manchester is leading DETERMINE with Dr Matthew Krebs as chief investigator and a team of leading clinical and scientific academics to develop the trial. Dr Lynley Marshall at the Royal Marsden Hospital is the paediatric lead, Dr Anshuman Chaturvedi at the Christie Hospital is the pathology lead, and both the translational lead Prof. Gary Middleton and statistical lead Prof. Lucinda Billingham are at the University of Birmingham. The trial also includes patient advocates Pete Burchill and Jacqui Gath, the latter recruited through the patient advocacy programme VOICE (Vision On Information, Confidence and Engagement), a joint initiative between Cancer Research UK and Independent Cancer Patients’ Voice. This inclusive patient-centred approach ensures that the patient perspective is represented, enhancing optimal trial design and implementation.   

The DETERMINE trial is currently open at various sites, including the Christie Hospital in Manchester, where the first patient was dosed in March 2023, as well as Oxford, Cambridge, Newcastle and Leicester. To ensure a diverse patient population and expand the reach of the trial, more sites are actively being opened across both the adult and paediatric Experimental Cancer Medicine Centres (ECMC) network, which is jointly funded by Cancer Research UK.  

To identify eligible patients, the Centre for Drug Development utilises existing screening programmes such as TARGET National, NHS Genomic Medicine Service, and Stratified Medicine Paediatrics. Led by Dr Matthew Krebs, TARGET National offers molecular profiling to people referred to the ECMC sites with advanced solid cancers, and the NHS Genomic Medicine Service offers genomic testing, including whole genome sequencing as part of routine care. The Stratified Medicine Paediatrics programme, run by the Institute of Cancer Research, sequences the tumours of children and young people with cancer. This use of existing infrastructure helps reduce pre-screening costs and improves the efficiency of patient recruitment. 

While Cancer Research UK plays a crucial role in fostering collaboration within its academic network, partnering with industry is essential for the success of DETERMINE. Cancer Research Horizons, Cancer Research UK’s innovation arm, bridges this gap between academia and industry. Our expertise in identifying and engaging commercial partnerships has already proved invaluable. Before DETERMINE launched in November 2022, the business development team secured a partnership with Roche to provide seven of their targeted drugs for evaluation across five treatment arms. In December 2022, Novartis joined the trial too. The team is actively engaged in discussions with additional partners to join the trial and create an extensive multi-pharma partnership.  

DETERMINE’s unique design means that any treatment that appears to be working for patients will be submitted for review by the Cancer Drugs Fund (CDF). The intention is that the CDF team, working with the NHS England Clinical Policy team, will then decide whether a period of data collection in the CDF is appropriate to assess if the drug could be used as a routine treatment option on the NHS for patients with this cancer type. 

Although the focus is to get new treatment options for patients on the NHS, the collaborative effort extends beyond the UK. The Centre for Drug Development and The University of Manchester are associate partners in the European Commission’s project, Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials (known as PRIME-ROSE). This project links DETERMINE to similar trials across Europe aiming to enhance patient access to precision cancer medicine by pooling data for statistical analysis that could support the approval of new treatment options. This is particularly crucial for rare cancers where gathering data is challenging. 

The value of the DETERMINE trial has already been recognised through two awards. The trial won the 2022 Bionow Healthcare Project of the Year Award for its innovative design and potential to help underserved patients. The Centre for Drug Development also received the Association of Clinical Data Management’s Team Excellence in the Management of Clinical Data Award for their contribution to DETERMINE. These accolades highlight the significance of collaboration in advancing rare cancer treatments.  

DETERMINE has had a remarkable year, but this is just the beginning. This award-winning trial demonstrates how Cancer Research UK and Cancer Research Horizons are pivotal in fostering collaboration between the public, private and charitable sectors that’s required to bring new treatments to those who need it. As the trial progresses and more partners join, the true value of collaboration will become evident. The horizon holds the promise of expanded treatment options and breakthroughs in cancer care for patients with rare cancers.