NIHRDataInsights/HRCSData huggingface dataset:
Title: CRUK/12/029: Tumours of the Choroid Plexus Epithelium, CPT-SIOP-2009, International Multidisciplinary Registry and Treatment Optimization Study for Patients with Choroid Plexus Tumours.
Funder: Cancer Research UK

Abstract: Background: Tumours of the choroid plexus epithelium are rare with the most_x000D_ frequently cited number for the total frequency being 0.5% of all brain-tumours in adults and children. If this estimation is correct, 1,500 to 2,000 patients will develop choroid plexus tumours per year around the world. Due to the low incidence of this tumour, only one randomised trial has ever been attempted. The treatment of choroid plexus tumours should include maximal possible surgery and there is some evidence that irradiation and chemotherapy can be helpful, but the specific role of chemotherapy remains unclear._x000D_ Aims: The overall aim is to improve choroid plexus tumour treatment through better understanding of the tumour biology and through increased knowledge about the benefit of specific treatment elements._x000D_ Methods: This is a multi-national phase III umbrella protocol incorporating registration of patients to a central database followed by stratified treatment including randomisation into one of four chemotherapy treatments, following maximal surgery informed by radiological diagnosis._x000D_ Initially, following surgery, patients will have tumour samples centrally reviewed before registering, where appropriate, to an international database. If the study algorithm calls for watch and wait, they are followed without treatment. The registry will provide a tool to describe the clinical presentation, metastatic pathways, disease progression, and survival of various choroid plexus tumours using a centralised international database._x000D_ If patients require adjuvant treatment either at diagnosis or at progression/recurrence, they will be randomised to a treatment protocol which aims to determine the effectiveness of four chemotherapy protocols at 24 months event free survival probability as well as providing toxicity data and feasibility data for each of the chemotherapy protocols, comparing three age groups of patients. Health related quality of life of patients will be measured and, where possible, tumour biological studies will be supported. The toxicity of radiation to central nervous system of young children will also be evaluated and the trial will provide a test of the Bayesian weeding design in a rare disease and an international study setting._x000D_ How the results of this research will be used: On a broad front, the research will provide information on the presentation of choroid plexus tumours and a mechanism in which to analyse the benefit of risk stratified treatment options. The treatment strategy associated with the best outcome will become standard therapy in due course.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Tumour Cell Death Laboratory
Funder: Cancer Research UK

Abstract: The aim of our group is to understand the factors regulating programmed cell death in cancer cells. Since it is known that inhibition of cell death mechanisms is a common event in tumour development, this poses problems for many forms of chemotherapy that utilise cell death pathways, leading to drug resistance. We are investigating both known cell death regulators as well as searching for novel proteins that control cell death and chemosensitivity. We envisage that the knowledge gained from our studies will be translated and lead to the improvement of existing clinical regimens or new targets for therapeutic intervention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/030: TRICON8 - Sample collection of ovarian cancer tissues and blood for translational research from patients participating in the CR-UK/MRC ICON8 trial
Funder: Cancer Research UK

Abstract: Background Ovarian cancer is the 4th most common cause of death from cancer in British women, with 40% 5-year survival. Most women will relapse after first-line treatment with surgery and chemotherapy. Improvements in treatment are still required. MRC ICON8 is a randomised phase III trial designed to investigate whether outcomes can be improved through chemotherapy dose-fractionation, by comparing the safety and efficacy of two, weekly carboplatin-paclitaxel regimens to standard 3-weekly treatment. It builds on evidence from a recent Japanese phase III trial that demonstrated significant improvement in progression-free survival using this approach. Weekly dosing increases dose-density and has anti-angiogenic effects in addition to cytotoxicity. ICON8 will recruit 1485 women with newly-diagnosed FIGO stage IC-IV epithelial ovarian, primary peritoneal and fallopian tube cancer over 3 years; and will be one of the largest ovarian cancer trials conducted. Aims 1. Establish a large, comprehensive biobank comprising tumour tissue, blood and serial plasma samples associated with fully-annotated correlative clinical data within the context of a randomised trial. This will be an invaluable resource for high-quality translational research in ovarian cancer, and will include the largest collection of paired pre/post chemotherapy-exposure tumour tissue (from women undergoing delayed primary surgery) yet assembled. 2. Enable specific research on predictive markers of resistance and response to dose-fractionated carboplatin-paclitaxel, and pharmacogenomics. 3. Provide a resource for other research, including collaborative projects. Methods Samples will be collected from all consenting UK trial participants including: (i)pre-treatment FFPE tumour tissue plus an additional resection sample in patients undergoing delayed surgery; (ii)whole blood for DNA extraction; (iii)longitudinal plasma samples, enabling assessment of circulating biomarkers. Blood and plasma will be stored for future use; tissue microarrays will be constructed and cores for RNA/DNA extraction taken. How the results of this research will be used Current proposals include use of FFPE and plasma to (i)investigate markers of resistance to platinum/taxanes in the context of dose-dense chemotherapy; (ii)evaluate markers of angiogenesis as predictors of response to weekly paclitaxel. Genomic DNA will be used to test hypotheses surrounding germline determinants of prognosis, treatment-response and toxicity. Applications to access samples will be invited.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium for ICGC Oesophegal Adenocarcinoma project
Funder: Cancer Research UK

Abstract: The esophageal project will focus on adenocarcinoma which is increasing in incidence in the UK and other developed countries and has a very poor outcome. The primary aims of this project are to deeply sequence tumour and normal genomic DNA (including the precursor condition Barrett’s esophagus when material is available) to provide a comprehensive catalogue of somatic mutations. This will be achieved through a UK-wide network of hospitals involved in a research collaboration called the OCCAMS consortium. The goal of this project is to use high quality clinical material with accurately annotated clinic-pathological, treatment and outcome data.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/12/030: MARS 2- A study to determine if it is feasible to recruit into a randomised trial comparing extended pleurectomy decortication versus no extended pleurectomy decortication in the multimodality management of patients with malignant pleural mesothelioma
Funder: Cancer Research UK

Abstract: Our study is designed to address the question if it is feasible to recruit to a trial of lung sparing surgery in addition to conventional chemotherapy in patients with malignant pleural mesothelioma. The 2011 National Lung Cancer Audit (2010 period) reported 2,023 patients diagnosed with malignant pleural mesothelioma in the UK and data from the 2011 Society of Cardiothoracic Surgeons Thoracic Surgery Database report (2010 period) reported 163 patients undergoing surgery with a “therapeutic” intent. Previous work by the same group (MARS1) reported that extrapleural pneumonectomy (removal of the entire lung, lining of the chest wall and diaphragm) within multimodality treatment for mesothelioma offered no benefit. However there has been an increase in interest in the application of a less extensive lung sparing operation (extended pleurectomy decortication) as some studies have suggested improved survival compared to the more extensive extra-pleural pneumonectomy. We plan to include all patients with mesothelioma (epitheliod and sarcomatoid) with disease confined to one hemithorax, deemed to be resectable and the patient deemed to be fit enough for surgery. Patients participating in the trial will receive 2 cycles of platinum and pemetrexed chemotherapy and a CT scan of the chest will be undertaken to screen for disease progression. Patients without any evidence of progression with be randomised to either (control arm) 4 cycles of platinum and pemetrexed chemotherapy or (intervention arm) extended pleurectomy decortication followed by 4 further cycles of platinum and pemetrexed chemotherapy. Patients will be followed up by 3 monthly clinic visits in the first 2 years and 6 monthly clinic visits from years 3 to 5. The initial study proposes to set up within 12 months and feasibility would be demonstrated by the randomisation of 50 patients or more by the end of the second year.


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: Improving Immunotherapy: Understanding and Predicting Protective Immune Responses in Cancer
Funder: Cancer Research UK

Abstract: Background: Immunotherapy has become a valid therapeutic option for solid tumours. However it remains unclear which patients will benefit, and how best to predict clinical outcomes. Tumour-infiltrating lymphocytes (TILs) are associated with extended survival in many cancers, arguing that clinical benefit is determined locally at the tumour site. The molecular phenotype that confers immune control is currently unknown. For cancer therapy, we need to establish additionally whether vaccination induces or expands epitope-specific T-cells and whether these can only be detected in the tumour bed or also in the circulation. Conversely, and in spite of the prognostic power of TILs, tumours develop multiple lines of defence against immune attack. We have demonstrated in head and neck squamous cell carcinomas (HNSCC) that a key feature of immune evasion is the presence of non-malignant myofibroblastic stromal cells. Aims: In our programme we wish to: 1) Determine the immune features of a clinically beneficial T-cell response, 2) Establish how the tumour stroma contributes to immune escape, 3) Determine how the observations from 1) and 2) determine the behaviour of antigen-specific imnmune responses. Methods: Towards these goals, we will initially define the characteristics of a predictive immune response in human papillomavirus (HPV)-driven HNSCC. Here we will exploit known HPV-derived TAA (E6, E7), and the uniformly excellent prognosis of HPV+ TILhigh patients to define the molecular signature of TIL at an mRNA level, followed by characterization of TAA specific T-cells. We will collaborate with Immatics Biotechnologies to identify peptide determinants that are visible to T cells by elution from frozen tumour. We will validate TAA candidates by characterising TAA-specific CD8+ TIL and will correlate local, regional and systemic, specific CD8+ T-cell responses with tissue features of immune regulation/immune escape. Clinical Translation: The knowledge gained from these studies will allow us to refine future immunotherapy trials, in terms of patient selection, monitoring and rational choice of vaccine/drug combinations.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Rho GTPase signalling in cancer invasion and metastasis
Funder: Cancer Research UK

Abstract: Background It is the metastatic spread of cancer cells that kills most cancer patients. Metastasis is a multi-step process, involving invasion of surrounding tissues, entry into and subsequent exit from the bloodstream or lymphatics, and proliferation in the new tissues. Rho GTPases contribute to cancer invasion and metastasis by regulating cytoskeletal and cell adhesion dynamics. We have carried out RNAi screens to identify key regulators of cancer cell migration, invasion and endothelial interaction. These screens identified multiple components of a Cdc42-centred signalling network, including Cdc42, the related Rho GTPases RhoH, RhoJ, RhoQ, RhoU and RhoV, their regulators and downstream targets. Although Cdc42 is well characterized for its effects on tumour cell invasion and metastasis, relatively little is known about how it is activated or which downstream targets contribute to these roles. In addition, Cdc42-related proteins act through similar targets to Cdc42, yet their involvement in cancer is understudied. Aims We propose that components of the Cdc42 signalling network are strong candidates for therapeutic intervention to reduce metastasis. We aim to: 1. Investigate how Cdc42 and its interacting partners affect cancer cell invasion and transendothelial migration (TEM) 2. Determine the roles of Cdc42 pathways in cancer metastasis in vivo. 3. Study how Cdc42-related GTPases contribute to cancer cell invasion and TEM. Methods 1: We will use biochemical and cell biological approaches to determine how Cdc42 and its binding partners identified in our RNAi screens regulate interaction with endothelial cells and invasion through extracellular matrix. We will focus particularly on their effects on adhesion receptors involved in these processes. 2: We will determine how key components of the Cdc42 signalling network affect cancer metastasis in vivo, using RNAi-mediated knockdown in mouse models. We will investigate the expression levels of Cdc42 and partners by immunohistochemistry in human prostate and breast cancer samples. 3: We will investigate how RhoH, RhoJ, RhoQ, RhoU and RhoV regulate cancer cell invasion and TEM using adhesion assays, timelapse microscopy and dynamic imaging of protein:protein interactions. We will determine how their interaction with their downstream targets contributes to cancer progression. We will also study the roles of these proteins in endothelial cells, and whether inhibiting them reduces cancer cell TEM. How the results of this research will be used Our results will provide important information on the mechanisms underlying cancer invasion and metastasis and thereby inform the development of new prognostic markers and therapeutic targets for cancer treatment.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Belfast Cancer Research UK Centres Core (Bridge Funding)
Funder: Cancer Research UK

Abstract: The Belfast Centre is a partnership between Queen's University Belfast and Belfast Health and Social Care NHS Trust and is based in the Centre for Cancer Research and Cell Biology (CCRCB) and the Clinical Cancer Centre. The Belfast ECMC will take an active role in the development and implementation of a UK-wide stratified medicines initiative for cancer treatment. Our translational research activity has been prioritized to address the crucial clinical questions within focused areas of disease while trials activity will be focused on innovative, biomarker-based protocols. Specifically, our programmatic aims will be to: 1) advance the discovery and implementation of novel biomarkers that aid earlier diagnosis of cancer, provide improved insights of a patient’s prognosis, or predict patient response to molecular-targeted therapies, 2) identify and validate novel targets for therapeutic intervention in poor prognosis disease sub-types exploiting pathology- and pre-clinical scientific expertise and resource, 3) prioritise patient recruitment to innovative clinical trials which prospectively aim to validate or apply accepted companion biomarkers, gene signatures and/or novel therapeutics, and 4) contribute fully to the development of the ECMC network.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);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
Title: Birmingham Cancer Research UK Centre Core (Bridge Funding)
Funder: Cancer Research UK

Abstract: As the first Cancer Research UK Centre, Birmingham will set the pace for national and international progress for genetics, gene therapy and the link between viruses and some cancers as well as focussing on cancers of the prostate and bladder and leukaemia. It will also become a leading centre for clinical trials. The Centre - a virtual framework - is a partnership between the University Hospitals Birmingham NHS Foundation Trust, the University of Birmingham and Cancer Research UK. Collaboration is the key to the success of the Centre which will also concentrate on large-scale population studies, cell biology and tumour immunology. The research community here already receive funding from Cancer Research UK but the Centre's initiative will increase the charity's contribution to supporting research in Birmingham to around ú9m a year. Cancer Research UK Centres aim to establish a nationwide network of excellence that will provide the best possible outcomes for patients by linking research activity with patient care and public engagement. Each Centre will focus on specific areas of research and aim to raise standards of care and forge links with local communities. The Centres's programme will enable Cancer Research UK to implement its research strategy and achieve its vision and purpose.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Southampton Cancer Research UK Centre Core (Bridge Funding)
Funder: Cancer Research UK

Abstract: Southampton has been designated one of Cancer Research UK's Clinical Centres. The centre has as its main focus the application of basic biology to the design and testing of new types of treatment for cancer. Our main areas of interest are in immunology, cell and molecular biology. The Centre incorporates the Cancer Research UK programme leaders: Professor Peter Johnson (Translational & Clinical Research) (Medical Oncology: translational and clinical research in lymphoma and lung cancer, antibody therapy) Professor Tim Elliott (Molecular and Cellular Immunology) (Immunology: Pathways of antigen processing, regulatory T-cells in tumour immunology) Professor Christian Ottensmeier (Translational & Clinical Research) (Medical Oncology: translational and clinical research in lung cancer and melanoma, DNA vaccines) Professor Graham Packham (Molecular Mechanisms) (Cell biology: regulation of programmed cell death in lymphoid and epithelial malignancies, novel small molecule therapeutics)


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: The lifetime effects, costs and cost-effectiveness of endometrial cancer screening
Funder: Cancer Research UK

Abstract: Background: Endometrial cancer is the fourth most common female cancer in the UK with 7,703 cases diagnosed in 2008. Currently there is no routine screening to diagnose this cancer. Transvaginal ultrasound (TVS) is a possible screening test. Recently, the diagnostic performance of TVS has been analysed using data from a large cohort study (48,230 women), nested within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS). This study found that TVS screening for endometrial cancer has good sensitivity in post-menopausal women and that the burden of false positive results can be reduced by limiting screening to higher risk groups. To date there has been little research on the cost-effectiveness of this intervention. Aim: To model the lifetime costs, effects and cost-effectiveness of alternative endometrial cancer screening strategies in the UK utilising data from the UKCTOCS study and other sources. Methods A Markov model will be developed to estimate the lifetime costs and effects in terms of quality adjusted life years of alternative endometrial cancer screening strategies. In line with the recommendations from the National Institute for Health and Clinical excellence a lifetime time horizon will be used and the perspective of the analysis will be that of the health service. Alternative strategies to be evaluated include screening with different tests, at different screening frequencies, age groups and specific consideration of screening for high risk groups. Currently there is little research on the costs of endometrial cancer in the UK. Data has been collected alongside the UKCTOCS on the health episode statsitics for all women. These data will be analysed to inform on the health service costs for women with endometrial cancer by stage. Data will be collected from UKCTOCS participants with endometrial cancer on their quality of life using the EQ-5D tool. The UKCTOCS trial provides a detailed analysis of the sensitivity and specificity of the TVS at different endometrial thickness thresholds and for different levels of risk. Data to inform other model parameters will be obtained from a structuted review of the literature. Uncertainty in model predictions will be explored fully in a range of sensitivity analyses. How this research will be used: Data from this modelling exercise will demonstrate to policy makers the potential effects, costs and cost-effectiveness of adopting an endometrial cancer screening programme. The modelling will be informative on refining the strategies: such as for high risk women which could be adopted at a National level.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS