NIHRDataInsights/HRCSData huggingface dataset:
Title: Cancer Research UK King's Health Partners Centre
Funder: Cancer Research UK

Abstract: Our CRUK King’s Health Partners Comprehensive Cancer Centre will foster excellence in discovery science to guide development of cancer biotherapies and hone their clinical impact. Focusing on the complexity of the tumour microenvironment and acknowledging this as a “Tumour Metropolis” (Theme 1) we will analyse permissive and inductive processes promoting tumour survival and expansion, thereby gaining the means to rebalance them in the clinic via the development and stratified application of biotherapies. To achieve this, we will draw upon wide-ranging fundamental cancer, allied medical and interdisciplinary research activities, supported by pillars of excellence in immunobiology, genetics, cell biology, clinical imaging and transplantation. Coupled to well-established biotherapeutics expertise (Theme 2), strengths in stratification (through profiling and imaging; Theme 3), and the clinical delivery of innovations through our ECMC, we will drive excellence from fundamental research into precision patient care, in complete alignment with CRUK strategy.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: PREDICT-Meso: PRE-malignant Drivers Combined with Target-Drug validation in Mesothelioma
Funder: Cancer Research UK

Abstract: Background Malignant Pleural Mesothelioma (MPM) is an incurable cancer that develops decades after inhalation of asbestos. Few treatment options exist and most patients die within a year. Multiple agents have disappointed in recent trials. The MPM tumour genome is dominated by tumour suppressor loss, a low mutational burden and few oncogenic drivers, posing major challenges for drug development. However, MPM is preceded by decades of pleural inflammation, providing a window of opportunity for precision prediction and early treatment. Our recent development of asbestos-dependent animal models has enabled longitudinal studies that reveal epigenomic events that precede MPM evolution. Similar longitudinal studies in humans could therefore effectively direct drug development, but have so far been impossible due to the lack of matched pre-MPM/MPM tissues. Aims PREDICT-Meso will build matched pre-MPM/MPM tissue cohorts and align these with the technologies and infrastructure needed to design effective therapies and evaluate these in future trials. We will determine: 1) How asbestos-driven chronic inflammation evolves into MPM, identifying the key molecular events and vulnerabilities 2) Whether individuals destined to develop MPM can be identified at a pre-malignant stage, and therefore recruited to future intervention studies using validated response tools. Methods Matched cohorts will be built by identifying MPM patients who present with preceding ‘Benign Asbestos Pleural Effusion (BAPE)’, which evolves into MPM in 12% of cases. A shared tissue bank will be interrogated using genomic, epigenomic, transcriptomic and immune landscape mapping. New patient-derived cell-lines, and organotypic models that reconstitute the macrophage population, will be developed using the same tissues. The effects of target-drug combinations will be assessed by high-throughput drug screening, and validated in vitro and in vivo, using an immunocompetent mouse model that combines intra-pleural asbestos injection with flexible induction of target MPM genes. BAPE patients recruited prospectively will undergo non-invasive (radiomic, proteomic, metabolic) risk-profiling and follow-up. Existing infrastructure will be leveraged to build critical serum and imaging cohorts for response marker validation. Data and knowledge will be shared via an open-access website, ICGC-ARGO, seminars and training schools and an international PhD training programme. How the results of this research will be used Validated target-drug combinations will feed into human clinical trials, using non-invasive risk prediction and response tools. PREDICT-Meso tissues, data and technologies will be shared, accelerating research in time to address an imminent global epidemic affecting the BRIC countries (Brazil, Russia, India, China), with whom critical links will be strengthened.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Deep conditioning using CRISPR edited T cells
Funder: Wellcome Trust

Abstract: T cells modified to express chimeric antigen receptors (CAR) have been successfully applied to treat B cell malignancies and are now being made more widely available as the first licenced products become available. The application of similar strategies against acute myeloid leukaemia have been challenging, in particular in infants and young children. Mortality is anticipated to be >70% for children who relapse after a first allogeneic transplant in high risk AML, and this reflects a failure to eliminate residual disease with chemotherapy or by anti-leukaemia transplant effects. We propose applying CRISPR base editing tools to generate ‘off the shelf’ T cells expressing CARs against different antigens and aim to secure deep molecular remission during pre-transplant conditioning in children who otherwise face a dismal prognosis. This application seeks to complete preclinical stage investigations of targeted base-conversion by cytidine deamination to disrupt critical genes required to overcome HLA-barriers and allow expression of CARs specific for shared T and myeloid lineage antigens. We propose translational advancement and rapid deployment into a Phase 1 trial in UK and Germany of the most effective available reagents to address unmet clinical need, while continuing development work on additional target antigens and improved editing tools.

Lay abstract: Acute myeloid leukaemia (AML) is a cancer of white blood cells and is treated with chemotherapy, followed by bone marrow transplant from a suitably matched donor. Unfortunately if AML persists through these treatments, the outlook is very poor, with most children succumbing to the disease. We have developed genome engineering techniques to collect and modify healthy donor immune cells (T cells) so that they don't need to be matched to a specific patient, but are armed against AML and can help clear out a patient's bone marrow. This form of 'deep conditioning' uses multiple CARs (Chimeric antigen receptors) to eliminate any AML cells remaining after chemotherapy, and this will then be followed by a second transplant to repopulate the blood and immune system. A similar approach has shown promise against other forms of leukaemia and we believe early application in the highest risk AML children is now justified.

Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK Clinical Trials Unit Glasgow
Funder: Cancer Research UK

Abstract: Background Clinical cancer research includes a variety of methodologies by which evidence is gathered from human subjects to enable the better understanding of cancer, its causes, its diagnosis and, most importantly, its treatment. By its nature, research carried out using human subjects must be done within a highly regulated framework to ensure ethical conduct, subject safety and a rigorous approach to data quality. Aims The aim of this programme is the continued provision of an infra-structure by which top quality clinical cancer research can be conducted across multiple centres and in multiple countries. Ultimately, the results of this research will change the way cancer is treated. Methods There are two components of activity for the Clinical Trials Unit (CTU) within this programme: 1. Support to clinical studies which are ongoing. This includes preparation of study protocols,successful submissions to Ethics, Regulatory Authorities and NHS permissions, setting up of research sites, co-ordination of trial data acquisition, management of project delivery-to-time, monitoring, pharmacovigilance, data management, analysis and publication of results. For many projects, some or all of these activities are funded by separate project grants with the CTU providing additional infrastructural resources. 2. The development of a programme of new clinical studies. These will include clinical trials from phases I to III exploring new drugs, new applications of old drugs, new forms of radiotherapy, surgery and supportive care. It also includes collaborative projects to enable the collection of tissue and biological materials from human subjects to facilitate the translation of laboratory findings to the clinic and vice-versa. There are several strategic themes within the proposed programme of work. These include gynaecological cancer,gastrointestinal cancer (in particular pancreatic cancer), genito-urinary cancer, and lung cancer. Although the main focus of the proposed work continues to be drug trials and translational medicine, we also plan trials using novel approaches in radiotherapy, and palliative care. Most of this work will be planned in conjunction with the clinical studies groups of the National Cancer Research Institute. Whilst feasibility work will be conducted entirely within the programme, applications will be made to grant-awarding bodies to fund specific trials. How the results of the research will be used Results from the proposed programme of work will be used to inform the design of future clinical trials or to change international clinical practice in the treatment of specific cancers.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Clinical Trials Unit, Birmingham
Funder: Cancer Research UK

Abstract: The University of Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU) is an internationally leading centre for the design and delivery of high-quality, practice-changing cancer trials across all age groups. Our overall aim is to effect change in clinical practice and improve care for patients with cancer. CRCTU’s Scientific Objectives are: 1. To extend the excellence of CRCTU’s trials portfolios including in: - National and International leadership of trials for childhood and adolescent cancers - National leadership in our Haematology and Stem Cell Transplant Trials Acceleration Programmes - Breast, lung, urological and head and neck cancers trials portfolios - New areas of unmet clinical need including brain tumours and hepato-biliary cancers - Our surgical trials programme 2. To increase the survival and quality of life of people diagnosed with cancer by developing innovative and biology-rich clinical trials including: - Development and implementation of efficient trial methodologies - Integration of translational research into clinical trials with a focus on biological stratification and novel biomarker discovery and validation CRCTU has coupled its out-standing strengths in clinical trials methodology with world-class scientific and clinical expertise to deliver state of the art clinical trials, nationally and internationally. Notably for stratified and personalised medicine through pioneering innovation in trial methodology and operational delivery of these complex trials. CRCTU is a leading international trials unit for children’s cancer and leukaemia trials. Responsible for the majority of academic childhood cancer trials in the UK, CRCTU will continue to drive the trials landscape to ensure children and young people have wide access to scientifically excellent, biology-rich clinical trials that will contribute to improved clinical practice in the UK and beyond. Our Trials Acceleration Programme (TAP) is rapidly advancing clinical evaluation of novel treatments for haematological malignancies through innovations in trial design and delivery. Our new programme, IMPACT, will also facilitate accelerated delivery of stem cell transplant trials in a nationwide network of UK transplant centres. The CRCTU continues to lead world-class trials portfolios in breast, lung, urological and head and neck cancers and is developing multi-disciplinary collaborations to address the needs of brain tumours and hepato-biliary cancers and integrating research in cancer surgery across the portfolio. CRCTU, a UK Clinical Research Collaboration-registered CTU, is in the vanguard of creating and delivering innovative strategies to accelerate the translation of scientific advances into improvements in cancer treatments that will benefit the lives of children, adolescents and adults diagnosed with cancer.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Centre for trials Research Cancer Group: Core funding QQR Wales Cancer Trials Unit and Haematology clinical Trials Unit
Funder: Cancer Research UK

Abstract: The CRUK core funded Cancer Group has been created within the Centre for Trials Research through the logical fusion of the Wales Cancer Trials Unit (WCTU) and the Haematology Clinical Trials Unit (HCTU). This Group represents the single largest component of a large national trials unit of approximately 140 staff, hosted by Cardiff University. Our vision: To deliver world class patient-centred clinical research that will enhance the lives of those affected by cancer. Our expertise, national and international collaborations will deliver on 3 major themes and one emerging theme: Haematological malignancy trials; building on international Acute Myeloid Leukaemia (AML) trials. o We will deliver practice changing international trials for patients with AML and will continue to innovate in this area, expanding to other haematological malignancies o Using our internationally leading methodology (Hills- “pick a winner” and “patient journey planner”) we will direct and disseminate methodological practice, both within our own portfolio and through collaboration, disseminate this skill (Marie Curie, Brain) o We will continue to optimise our translational research, delivering improved outcomes for patients, expanding our work on minimal residual disease as well as disease relapse/resistance (AML-biobanking- Ottmann, Hills) Multi-modality precision therapy trials: o We will deliver practice changing clinical trials using a range of methodological approaches, taking a national leadership role in CRUK cancers of unmet need (oesophagus) o We will continue to optimise our collaborations to improve our methodologies for these complex intervention trials, in which we have national leadership (Hurt) o We will further optimise and expand our translational and ancillary studies, with a focus on imaging as a biomarker and radiotherapy delivery (Spezi- radiomics, Marshall- PET, CUBRIC- MRI). Novel and Contemporary methodology trials: o We will deliver nationally and internationally leading methodologies for our trials portfolio, including embedded methodological innovation/evaluation o We will cultivate national networks and partnerships to deliver innovative cost effective trial designs in platform based studies incorporating early phase trials. o We will prioritise scientifically rich studies, with a focus on biology and imaging, maximising what we can learn from our patients With this focus we will utilise our CRUK core funding to deliver the CRUK research aims in collaboration with the UK network of CTUs and the broader cancer research community. To create the foundation for our future looking CTU, during this QQR we have undertaken significant restructuring, to enhance our scientific expertise, breadth, efficiency and resilience.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/19/011 COLO-PREVENT; A platform for developing COLOrectal cancer PREVENTion therapies
Funder: Cancer Research UK

Abstract: Background Colorectal cancer (CRC) is the second most common cause of cancer death in the UK. Population aging and the increase in obesity and type 2 diabetes, both risk factors for CRC, are likely to magnify the problem in future decades. Prevention, through the use of safe and effective therapies offers a largely untapped strategy for reducing the incidence and mortality due to CRC. Such therapies could be employed for primary prevention, and in conjunction with screening programmes in patients considered ‘high-risk’ due to the detection of premalignant adenomas. COLO-PREVENT is a unique multicentre phase 2/3 trial platform for evaluating the efficacy of cancer preventive therapies that is embedded within the Bowel Cancer Screening Programme. It will recruit patients deemed ‘high-risk’ for the development of metachronous colorectal polyps and/or cancer after clearing colonoscopy. Aims: 1. To determine whether metformin plus aspirin is superior to aspirin alone. 2. To assess whether resveratrol has any effect on polyp recurrence and identify the most active dose in a signal-seeking trial. Methods The design of COLO-PREVENT is based on the seAFOod trial, which was the first CTIMP carried out in the English BCSP and which established protocols and RCT infrastructure at screening sites. BCSP patients aged between 55–73.5 years, identified according to BCSP criteria as ‘high-risk’ at the first complete screening colonoscopy, will be randomised to aspirin (Standard of Care) or aspirin plus metformin for three years. For the parallel resveratrol signal-seeking phase 2 trial, participants either already on, or intolerant to aspirin or metformin, will be randomised to two doses of resveratrol or placebo for 12 months. The primary endpoint is adenoma recurrence (MAP), secondary endpoints include adenoma detection rate (ADR), advanced adenomas, adenoma subtype and location, adverse events and compliance. Research endpoints will focus on the association between metabolic status and treatment efficacy, assessment of pharmacodynamic biomarkers and role of the gut microbiome in predicting and mediating the effects of the three therapies. How the results of this research will be used. We anticipate our results will identify a number of safe effective therapies that can be used in conjunction with screening to prevent polyp recurrence and ultimately decrease CRC risk. Inclusion of the sub-trial is an innovative way to establish a pipeline for testing other promising therapies and interventions, generating the first evidence of clinical efficacy. COLOPREVENT will provide a long-term platform for testing therapies, other lifestyle/behavioural interventions and novel combinations.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: Cancer Clinical Trials in the Cancer Research UK and UCL Cancer Trials Centre
Funder: Cancer Research UK

Abstract: The CR-UK and UCL Cancer Trials Centre (CTC) has a broad portfolio of studies, and is part of the UCL Cancer Institute and the Institute of Clinical Trials and Methodology at UCL. Our aims are to improve survival and quality of life, and increase knowledge of cancer biology by evaluating new therapies and biological/imaging markers, and find ways of diagnosing cancer earlier. Our main areas of interest are haematological malignancies (lymphoma, leukaemia and myeloma), gynaecological, lung, head & neck, and gastrointestinal cancers but we also conduct studies in and prostate cancers and sarcomas. We have established expertise in phase I to III trials and observational studies. Our interventional clinical trials evaluate new agents including ATIMPs, licensed and unlicensed drugs, radiotherapy, surgery and imaging. Most are multi-centre studies, and several have international collaborating sites. Staff from UCL Partner organisations lead 60% of our studies, the others originate from national or international investigators. Over the last 15 years we have built an infrastructure of highly skilled staff, working with clinical academics to develop studies, from concept, through funding and set-up to execution, data analysis and publication. We have staff skilled in statistical design (including Bayesian methodologies) and analysis, clinical trial regulations and trial leadership; and a national role in training CTU staff. During the last 5 years we have opened 41 new studies, and enrolled more than 6400 patients. We have published 155 peer-reviewed articles and made practice-changing contributions to the treatment of lymphoma, leukaemias, biliary tract, thyroid, anal and lung cancers; and significantly advanced our understanding of lung cancer genomics. We have significant local and national collaborations with other universities and CR-UK Centres, and have a strong record of data sharing. Our PPI is expanding through local links, charities and the NCRI. Several CTC staff are members of the NCRI CSGs and UKCRC CTU groups, and have had direct input into national/international trial conduct initiatives. Our strategy is to use the core infrastructure to leverage significant funding from other sources including industry. We will continue to conduct innovative studies with integrated translational research, and work with CR-UK’s Cancer Research Technology and UCL Business to commercialise products or methodologies arising from our projects. Our major research areas will be genomic evolution studies linked to biomarker-directed treatment trials, large-scale international trials in ovarian cancer and acute leukaemia, a programme of early phase immunotherapy studies and population lung cancer screening.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS