Developing Existing Healthcare Technologies to Deliver More Affordable and Effective Cancer Care

Lead Research Organisation: University College London

Abstract

Our aim is to reduce cancer deaths and the side effects associated with cancer treatments. We design clinical trials and other research studies that test several new approaches at the same time. This speeds up the evaluation of new therapies.

Cancer is becoming more common, especially in low and middle income countries (LMICs) where it is estimated that 70% of cancers and 80% of cancer deaths will occur in 2020. We focus on the need for more affordable and effective cancer treatments. This is also important for high income countries.

We test drugs that are already used for another disease. This is called repurposing. We also test whether radiotherapy, surgery and existing scanning techniques can be used in different and more efficient ways to improve the diagnosis and treatment of cancer. We will also test whether newer drugs (immuno–oncology) can be given for shorter periods of time with the same benefits and less side effects.

In the future we will work on: a) cancers that are common and cause many deaths in LMICs; b) cancers that are less common which makes it difficult to run clinical trials; and c) studies to prevent cancer. Running a clinical trial in these areas can be challenging and not many research groups work in these areas.

The impact of our work is recognised if the treatments we assess are recommended for patients by doctors because of our trials. Further impacts are to help increase research visibility and capacity in LMICs, including for example heling to develop Principal Investigators in countries. We also collect biological samples from trial participants and scientists evaluate them to increase our understanding of cancer.

Technical Summary

Our aim is to improve cancer survival and decrease cancer morbidity by designing and implementing innovative late phase studies that have a major impact on clinical practice. We focus on adaptive trials that test more than one primary research hypothesis to increase efficiency including multi-arm multi-stage platforms, umbrella, and basket trial designs, primarily in the phase III setting.

Cancer incidence is increasing rapidly, and disproportionately so in low and middle income countries (LMICs) where it is estimated that 70% of cancers and 80% of cancer deaths will occur in 2020. This programme focusses on the need for affordable and less toxic therapies that can be implemented across a range of economic settings. We evaluate existing healthcare technologies (e.g. drug repurposing or rescheduling, established imaging techniques, surgery and radiotherapy) to optimise clinical efficacy and/or broaden the patient group that can benefit.

We address clinical questions others are unlikely to tackle, either due to a challenging clinical scenario, geographical setting, and/or lack of interest or support from the pharmaceutical industry. Consequently, and particularly in the future, we will focus on: a) cancers with a high incidence and mortality in LMICs; b) rarer and less common cancers; and c) prevention and early diagnosis as an affordable approach to improve outcomes. Integrated working with methodology colleagues enhances trial design, conduct and analysis, and facilitates the implementation of results.

Examples of drug repurposing projects include the evaluation of aspirin as an adjuvant therapy in common solid tumours and metformin as a potential anti-cancer therapy. Immuno-oncology projects are focussed on shorter and more affordable regimens and are underpinned by novel trial designs developed at the MRC CTU. Primary prevention cancer trials are long term projects; our aim is to conduct them efficiently, making optimal use of electronic health records.

We are developing an increasing network of investigators in LMICs - integral to this work is our capacity building activities in terms of education and mentorship in clinical research methodology, particularly in India. Impact is recognised by change in clinical practice and incorporation of the new clinical approach into international guidelines.

Maximising the potential between discovery science and applied research is key to our strategy with biological samples from trial participants analysed by cutting edge scientists and, where appropriate, results fed back into clinical practice and future trial designs. We are also building upon our trial work particularly in prostate cancer and our aspirin-related studies to establish repositories of trial data to facilitate meta-analyses.

Publications

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Ebert M (2022) In Regard to Shortall et al in International Journal of Radiation Oncology*Biology*Physics

 
Description CRUK/06/001: PATCH: Prostate Adenocarcinoma: TransCutaneous Hormones - 2021 extension
Amount £592,034 (GBP)
Funding ID C471/A12443 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 09/2024
 
Description REFINE stage I/II funding, Jon Moulton
Amount £1,061,788 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2020 
End 04/2024
 
Description Research Careers Committee - Clinical Trial Fellowship - November 2021 - Dr Sophie Merrick
Amount £150,581 (GBP)
Funding ID RCCCTF-Nov21\100002 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2022 
End 12/2025
 
Title PATCH trial sample storage 
Description In PATCH, blood and urine samples were collected at randomisation and various time points during trial follow-up for consenting patients randomised up to end October 2013. Baseline blood samples for future research are also being collected in all consenting patients (before and after October 2013). Until September 2021, all samples were stored at Charing Cross Hospital Assay Laboratory. In September 2021, samples were transferred to the Biodock biobank in Nottingham. 
Type Of Material Biological samples 
Year Produced 2006 
Provided To Others? No  
Impact These samples will be utilised in analyses to increase understanding of the underlying mechanisms for the potential benefits and adverse effects of the trial treatments, for example, for assessing changes in SHBG, oestrone/oestradiol ratio and bone biomarkers during time on treatment. 
 
Description REFINE translational samples - storage and analysis (NIH) 
Organisation National Institutes of Health (NIH)
Department National Cancer Institute (NCI)
Country United States 
Sector Public 
PI Contribution Within REFINE, blood samples are taken prior to each treatment administration. The aims are to better understand both the pharmacokinetics of immune checkpoint inhibitors and also the pharmacodynamics with respect to target efficacy between different frequencies of administration. These samples will initially be stored at Imperial College in the UK, before being transferred to Dr Cody Peer and Dr William Figg at the National Cancer Institute for analysis.
Collaborator Contribution The expertise of the NIH, and in particular Drs Peer and Figg, is key to the analysis of the trial samples, and the interpretation of the results.
Impact REFINE is in the final stages of set-up, so no outputs yet.
Start Year 2022
 
Description Training the next generation of Indian clinical trialists 
Organisation Christian Medical College, Vellore
Country India 
Sector Academic/University 
PI Contribution Co-I
Collaborator Contribution PI
Impact No outputs yet. Multidisciplinary - clinicians, statisticians, clinical trialists,
Start Year 2021
 
Description Training the next generation of Indian clinical trialists 
Organisation Translational Health Science And Technology Institute
Country India 
Sector Public 
PI Contribution Co-I
Collaborator Contribution PI
Impact No outputs yet. Multidisciplinary - clinicians, statisticians, clinical trialists,
Start Year 2021