NIHRDataInsights/HRCSData huggingface dataset:
Title: Cardiff ECMC
Funder: Cancer Research UK

Abstract: The Cardiff ECMC strategy will have particular focus on our areas of expertise (molecular characterisation of bio-samples for patient stratification; pre-clinical drug testing; trials methodology; early phase trials delivery) across our main tumour-types of interest (breast, colon, haematological). Our ECMC will unite our translational research in both solid tumours and haematological malignancies, bringing together our efforts in shared Focus Areas - Trials, Stratified Medicine and Drug Development, as part of a “translational loop” of pre-clinical and clinical research. We will consolidate our unique position amongst the few ECMCs with a clear focus on haematological malignancies, with a national leading role in the design of trials in Acute Myeloid Leukaemia (AML), broadening our activity in haematological malignancies to include Acute Lymphoblastic Leukaemia (ALL), myeloma and cellular therapies. We will retain focus on existing strengths in pre-clinical drug-testing and innovative trials methodology in haematological malignancies, which has driven the UK’s national portfolio of trials in AML and in stratified medicine trials for solid tumours. We will exploit our increased capacity for Phase I trials activity, developed in the latter stages of the last quinquennium, to increase flow through our established therapeutic translational pipeline. New foci for our Phase I trials activity will include trials for minimal residual disease, drug:radiotherapy combination studies and immunotherapy. In addition, we will increase the flow of innovative, home-grown trials of novel therapies towards funding bids from CRUK’s New Agents Committee, via our innovative translational research committee and Cardiff University’s Centre for Trials Research, which incorporates our Haematology Clinical Trials Unit and CRUK-funded Wales Cancer Trials Unit. In the coming quinquennium, the strategy for our ECMC will be clearly aligned with those of the Cardiff University College of Biomedical and Life Science’s Cancer Research Theme and the Wales Cancer Research Centre, offering for the first time a fully integrated Cardiff cancer research strategy, as the driving force of the Wales Cancer Partnership. It will be underpinned by our ambition to expand our cancer research capacity and develop the next generation of cancer research leaders.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: ECMC Paediatric Network
Funder: Cancer Research UK

Abstract: The paediatric ECMC network is a co-ordinated and efficiently functioning network, recognised internationally, that has significantly increased the numbers of early phase trials available to children in the UK. The network has increased recruitment to pharmacology studies, and disseminated expertise in functional imaging. We now propose an expanded network with two new centres bringing additional expertise in immunotherapy and translational research, and broadening our coverage of the UK. The centres will be grouped into 4 larger regional networks, with a central network manager. Each regional network will contain a critical patient mass, and at least one “first in child” centre; and we propose to open all early phase trials in each network. This new structure will increase the attractiveness of the UK for early phase trial work, both for academic and industry sponsors, offering a co-ordinated network for rapid identification and recruitment of increasingly tightly defined groups of patients. The paediatric network will continue to collaborate with the Birmingham Clinical Trial Unit to develop innovative approaches that allow effective novel agents to be brought rapidly to the clinic for patient benefit. The expanded network will provide the robust infrastructure needed for treatment of childhood cancer in the UK to be progressed to the next level. The network will facilitate collection of biological material for rapid genomic testing, for biomarker assessment, and for pharmacology studies. This infrastructure will allow the UK to operate as a full partner in international precision medicine initiatives addressing areas of significant unmet need, and to continue to take leading roles in European initiatives to improve access to novel agents. The networks will also co-ordinate the review of patients at relapse, ensuring that tumour material has been sequenced for actionable mutations, and that all therapeutic options have been offered to the child and family. This strategy will ensure equitable access of all children to novel treatments, regardless of where they live in the UK. Finally the proposal will link excellent translational research more firmly to the clinic, smoothing the flow of promising novel therapies from laboratory models to children, and allowing a direct two way interaction that will produce rapid refinements in novel agents for the benefit of patients. Ultimately by facilitating the development of better treatment for patients at relapse, the paediatric network ECMC will contribute to the improvement of treatment for childhood cancer as a whole.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Lung Cancer Centre of Excellence Supplementary Award
Funder: Cancer Research UK

Abstract: [From main award]: The establishment of the CRUK Lung Cancer Centre of Excellence at Manchester and UCL brings together a unique range of internationally renowned scientists and clinicians within the field of lung cancer research. By building on this existing foundation, we will create an environment that catalyses imaginative and innovative lung cancer research. The Centre combines expertise in basic, translational and clinical research, which is focused around eight complementary and interacting themes: Basic Science, Immunology, Drug Discovery, Early Detection and Pre-Invasive Disease, Tumour Evolution and Heterogeneity, Biomarkers, Clinical Trials and Radiation Biology/Radiotherapy Trials. We are committed to delivering an outstanding lung cancer training programme and building a world class centre of excellence in lung cancer research. The establishment of the CRUK Lung Cancer Centre of Excellence at Manchester and UCL recognises our strong track record, expertise and ambition in all aspects of lung cancer research. By working together, we have a real and exciting opportunity to support advances in the prevention, diagnosis, treatment and care of lung cancer; with our ultimate aim to improve outcomes for lung cancer patients. (http://www.cruklungcentre.org/About-Us/About-Us)


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: ICGC ARGO
Funder: Cancer Research UK

Abstract: ICGC-ARGO’s mission is to provide the world with a million patient years of precision oncology knowledge.

Lay abstract: ICGC-ARGO’s mission is to provide the world with a million patient years of precision oncology knowledge.

Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: AURORA: Atezolizumab in patients with squamous cell carcinoma of the bladder and urinary tract – a single arm, open label, multicentre, phase II trial
Funder: Cancer Research UK

Abstract: Background Bladder and urinary tract cancers account for ~10,000 new diagnoses and ~5,000 deaths annually in the UK. 90% are transitional cell carcinomas (TCC) for which advanced disease is treated with platinum based chemotherapy and PD1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease setting. We have yet to establish definitive systemic treatment options for advanced UTSCC, which responds poorly to chemotherapy or radiotherapy. UTSCC patients are frequently disenfranchised by exclusion from TCC clinical trials, including registration studies for immunotherapy. Our preliminary data, from a retrospective cohort with UTSCC, indicate high PDL1 expression and tumour infiltrating lymphocytes (TIL) in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy. Aims The AURORA trial will test the hypothesis that PD-L1 inhibition with atezolizumab is active, tolerable and safe, in UTSCC. We will incorporated comprehensive translational research components, to allow prospective investigation of the immune-biology of the disease and potential biomarkers of treatment response. Methods Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy for one year if tolerated. The primary endpoint is best overall response rate (ORR, by RECIST v1.1). AURORA has a single arm, Simon 2 stage, statistical design, to allow an independently assessed interim review of efficacy. We will recruit up to 33 patients with SCC histology UTC. If 4 or more, of the first 19 patients (Stage 1), achieve an objective radiological response (RECIST v1.1) then the trial will continue to stage 2 where 8 or more responses in 33 patients will meet the criteria to indicate further investigation is warranted (p1=15%, p2=35%, 1-sided alpha=0.1, power=90%). Secondary endpoints will include overall survival, progression free survival, duration of response, response using irRECIST, quality of life, safety and tolerability (CTCAEv5) and evaluation of potential biomarkers of treatment response. How the results will be used AURORA would represent the first prospective trial of immunotherapy in UTSCC and only the second dedicated study of any systemic therapy. If successful, we hope to define a standard of care approach to intervention for this patient group. The trial is supported by the NCRI Bladder and Renal Group, the International Rare Cancers Initiative and UK patient groups.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Integrative Cancer Epidemiology Programme: Towards improved causal evidence and enhanced prediction of cancer risk and survival - Studentship
Funder: Cancer Research UK

Abstract: Our Cancer Research UK (CRUK)-funded 4-year PhD programme will equip the next generation of inter-disciplinary researchers with the scientific skills to exploit the wealth of new data being generated in population health sciences. Our innovative four-year PhD programme offers students the opportunity to develop the knowledge and technical skills to become future research leaders in the field of cancer epidemiology. The PhD programme is based at the University of Bristol’s Medical School, a leading centre for research and teaching in Population and Translational Health Sciences. It is embedded within our CRUK Integrative Cancer Epidemiology Programme (ICEP), and combines tailored innovative training in a foundation year (year 1), followed by a three-year PhD project (years 2-4) chosen to suit the interests of each student. Towards the end of each studentship a range of training opportunities are available to support the transition into the next stage of an individual's career. Research visits to other organisations within and beyond the UK, such as to our collaborators at the International Agency for Research in Cancer, McGill University or the Quadrum Institute, are actively encouraged, along with participation in conferences, workshops and other events. Students will benefit from a cross-disciplinary programme of cancer research in Bristol, ranging from increasing our fundamental understanding of the molecular and cellular basis of cancer, to ICEP’s focus on cancer aetiology, detection, risk prediction, genetic epidemiology, population-based genomics and bioinformatics. Our mission is to successfully translate basic biology cell discoveries into potential interventions to prevent, detect or treat cancer. We welcome students from a wide range of scientific backgrounds. Our community of researchers have diverse skills and work together on exciting interdisciplinary research projects using data and samples from leading cohort studies such as ALSPAC and UK Biobank and cancer studies such as ProtecT and Head & Neck 5000. We strongly encourage applicants from a range of disciplines (e.g. natural sciences, biostatistics, molecular genetics, econometrics, biochemistry, mathematics, statistics, engineering and computer science). Our PhD programme and training environment is designed to provide students with the necessary skills to succeed in this field.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: CRUK/13/026: CompARE: Phase III randomised controlled trial Comparing Alternative Regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer
Funder: Cancer Research UK

Abstract: BACKGROUND: Oropharyngeal cancer (OPC) incidence is increasing dramatically, especially in the Western World, and is caused by the Human Papillomavirus (HPV). Recent research shows 3 risk groups: low, intermediate and high-risk groups with 3-year overall survival of 93%, 71% and 48% respectively. Consequently, new treatment paradigms are being considered. Since both intermediate and high-risk groups do not demonstrate the high survival rates achieved by their low-risk counterparts, both clinicians and patient groups have called for treatment intensification to improve loco-regional control and overall survival. OBJECTIVES: 1. Examine outcomes of alternative treatments aiming to improve survival in intermediate and high-risk OPC. 2. Compare quality of life (QoL), functional and toxicity outcomes and cost effectiveness of these alternative treatments. DESIGN: Pragmatic Phase-III randomised controlled trial using an efficient, adaptive multi-modal multi-stage (MAMS) design, with an integrated qualitative recruitment study aiming to optimise recruitment and consenting. POPULATION 627 intermediate and high-risk OPC patients. TREATMENT ARMS: Treatments are intensified by adding more chemotherapy, more radiotherapy or surgery to the current standard concomitant chemoradiotherapy: Arm 1: Control: Concomitant chemoradiotherapy – cisplatin and radiotherapy 70Gy in 35F. Arm 2: Resection of primary + neck dissection followed by Arm 1. Arm 3: Induction chemotherapy using docetaxel + cisplatin + 5-fluorouracil (TPF) followed by Arm 1. Arm 4: Dose-escalated radiotherapy using IMRT+ Concomitant cisplatin. ASSESSMENTS: 1. Examination + CT scanning 3 months following treatment end. 2. Death, recurrence and toxicity - follow-up monthly first year and 2-monthly second year. 3. QoL and swallowing questionnaires at baseline, treatment-end, 6,12 and 24 months. OUTCOME MEASURES AND ENDPOINTS: Primary Definitive (efficacy) endpoint: Overall survival time. Interim (activity stages): Disease free survival time. Secondary 1. Progression free survival (interim activity endpoint). 2. Total number of severe (grade 3-5) acute and late toxicity events at 2 years, using CTCAE version 4.0. 3. Overall and head-neck specific QoL at 24 months, using EORTC C30/HN35 questionnaires. 4. Swallowing, using MDADI questionnaire PEG-use at 24 months. 5. Cost effectiveness using EQ-5D, patient diaries and primary and secondary resource utilisation data. 6. Surgical complication rates. HOW WILL RESULTS BE USED: This groundbreaking study will determine and establish the international standard of care for this large group of patients, whose current treatment outcomes are in need of improvement. This study is supported by NCRI Head Neck CSG and 2 national patient support groups.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Deciphering the microenvironmental niches of lung cancer evolution
Funder: Cancer Research UK

Abstract: Background A major therapeutic obstacle in lung cancer, the leading cause of cancer-related death worldwide, is its evolution leading to drug resistance. Cancer evolution is often studied without considering its microenvironmental dependencies or niches, which are fundamental to understanding cancer fitness, adaptation and selection. Such knowledge will direct therapeutic interventions to alter or remove the selective pressures driving evolution of resistance. Thus far the role of microenvironmental niches in shaping cancer evolution is poorly understood, due to high levels of spatial and molecular heterogeneity in human tumours. Aims I propose to overcome this challenge by enabling large-scale automated histology image analysis in the largest cancer evolution study to date, TRACERx. I have pioneered the use of rigorous statistical analysis in quantitative histology to dissect the spatial heterogeneity of the microenvironment. I will develop new approaches that combine such methods with multi-region sequencing, aided by ecological concepts, to advance our understanding of lung tumours as evolving ecological systems. Methods I will test the central hypothesis that microenvironmental niches drive lung cancer evolution, by 1) inferring niches as microenvironmental characteristics surrounding cancer; 2) identifying niches predictive of clinical outcome and sensitivity to immunotherapy, chemotherapy and targeted therapies; 3) establishing how niches shape the evolution of cancer diversity and treatment resistance, and identifying molecular targets to disrupt these niches. How these results will be used My novel approaches to studying cancer evolution in the spatial context of its microenvironment in a unified ecological framework, powered by large-scale analysis of human tumours, will offer new breakthroughs in identifying selective pressures driving lung cancer evolution through the course of therapies, thereby identifying new biomarkers to guide therapies and novel treatment strategies that exploit the ecological dependencies of lung cancer.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Grid Oncology: Remaking Cancer Care in India
Funder: Wellcome Trust

Abstract: Cancer has been recognized as an important and growing public health concern in low- and middle-income countries. In India, the annual number of new cases is projected to increase to almost 2 million over the next 15 years. In 2012 India’s flagship cancer hospital, Tata Memorial in Mumbai, made a step change and responded to the rapidly growing number of patients. Supported by other public sector cancer centres, Tata Memorial launched the National Cancer Grid of India to decentralize, standardize and digitalize oncology. Since 2012, 150 centres have joined the grid, covering 60% of all cancer patients in the country. The proposed project will analyse the emergence of the grid as a powerful new actor that seeks to redraw the map of cancer care in India. It investigates how the idea of grid oncology is put into practice and shows how it matters for patients, practitioners and policy-makers. Three key research questions guide the project: 1. What becomes of oncology once it finds itself under the spell of a grid imaginary? 2. How is oncology decentralized, standardized and digitalized and what are the potential dangers? 3. What understandings of knowledge, medicine and expertise are at stake in grid oncology?

Lay abstract: In 2012 India’s flagship cancer hospital, Tata Memorial in Mumbai responded to the rapidly growing number of patients and launched a network of cancer centres. The National Cancer Grid of India was established to decentralize, standardize and digitalize oncology and develop new forms of treatment relevant for low- and middle-income countries. The proposed project will analyse the emergence of the grid as a powerful new actor that seeks to redraw the map of cancer care in India. We will use anthropological research methods to analyse how the grid seeks to transform oncology for the benefit of patients.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/14/040 ADSCaN - A Randomised Phase II study of Accelerated, Dose escalated, Sequential Chemo-radiotherapy in Non Small Cell Lung Cancer
Funder: Cancer Research UK

Abstract: Background: Lung cancer is the most common cause of cancer mortality in the UK. In the year 2002 there were 38,410 new cases and 33,602 deaths. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. The majority of cases are inoperable at presentation but many patients with stage I-III disease can still be treated radically using radiotherapy, although survival rates are disappointing. Successful local control has been found to correlate with improved survival (Auperin JCO 2010). Strategies to achieve improved local control rely on intensification of the local anti-tumour effect though radiation sensitization, acceleration of the RT schedule or dose escalation. As the majority of patients are not suitable for the gold standard treatment of concurrent chemo-radiotherapy (CTRT), novel strategies integrating RT technological advances and radiobiological knowledge need to be evaluated in the group of patients treated with the alternative treatment option of sequential CTRT. Therefore, the UK strategy has been to develop separate escalation protocols for hyper-fractionated and once daily schedules (CHARTED, IDEALRT, ISTART, and Isotoxic IMRT) Aim of Study: This aim of the study is to identify the most promising of 4 dose escalated accelerated sequential chemo-radiotherapy schedules (CHARTED, IDEAL, I-START, Isotoxic IMRT) to take forward to test in a phase III study against standard sequential chemo-radiotherapy. The selection of a single schedule is required to make an appropriately powered phase III feasible. Method: A randomised phase II screening/”pick-the-winner” design will be used to identify which of the 4 schedules appear to have better survival outcomes than standard sequential chemo-radiotherapy. A final selection will be made between arms that pass this criteria based on all the available date (efficacy, toxicity, quality of life and health economic data). A novel design will be used that will allow individual centres to randomise to only one (but more if they have the resource) of the experimental schedules. All centres will randomise patients to the standard arm. How the results will be used: The results of this trial will be used to take forward a single sequential chemo-radiotherapy schedule for further testing in a randomised phase III trial.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS