NIHRDataInsights/HRCSData huggingface dataset:
Title: CRUKE/10/019: ICE: A Phase II trial of the addition of Ipilimumab to Carboplatin and Etoposide chemotherapy for the first line treatment of extensive stage small cell lung cancer
Funder: Cancer Research UK

Abstract: Small cell lung cancer (SCLC) is a malignancy with initial good response to systemic therapy, but with very poor long term outlook. Patients who present with paraneoplastic autoimmunity achieve better long term survival apparently independently of tumour load at presentation. Ipilimumab is an anti-CTLA4 antibody, which has been shown to induce anti-tumour immune response to tumour derived antigens. The study will be a single arm phase II study. Standard chemotherapy with Carboplatin and Etoposide will be given up to 6 times at 3 weekly intervals. Ipilimumab will be added to the 1st and 4th cycle followed by up to four doses of 3 monthly maintenance ipilimumab. The study will recruit patients with extensive stage small cell lung cancer without clinical evidence of paraneoplastic autoimmunity. This study explores the hypothesis that the edition of ipilimumab to conventional chemotherapy for SCLC will generate an effective immune response to tumour driven antigens, released during chemotherapy, and that will result in improved outcome. The study also aims to establish the toxicity of this combination, particularly neurotoxicity, given that the naturally occuring SCLC association, paraneoplastic autoimmune phenomena mainly affect the nervous system. In the translational element of this trial we wish to establish the immunological basis underlying ipilimumab activity in this setting, with a focus on neuronal antigens.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: GROMITS: Genetic Regulation Of Myeloma In Tissue Samples
Funder: Cancer Research UK

Abstract: Background to the proposal: Myeloma XI is a randomised phase III clinical trial exploring the role of two new drugs, lenalidomide and bortezomib, for the treatment of newly diagnosed multiple myeloma. Specific aims of the research: The aim of this project is to establish a sample bank linked to the clinical trial which will allow for the identification and validation of biological prognostic markers. Summary of proposed study: Following informed consent the excess tissue from diagnostic peripheral blood (PB) and bone marrow (BM) aspirate samples will be obtained from myeloma patients entered into the myeloma XI clinical study.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/020: COPERNICUS: Chemotherapy with or without Panitumumab then Radiation then Immediate Curative Surgery for operable rectal cancer
Funder: Cancer Research UK

Abstract: Chemotherapy with or without Panutumimab then radiation then radiation with immediate curative surgery for operable rectal cancer


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/032: NITRO trial: Neoadjuvant IntraviTreal Ranibizumab treatment in high risk Ocular melanoma patients: A two stage single centre Phase II single arm study.
Funder: Cancer Research UK

Abstract: Background Uveal melanomas have an incidence of 6 per million per year, of which our experienced multidisciplinary Liverpool Ocular Oncology Centre (www.eyetumour.com) treats approximately 250-300 new patients per year. Without treatment, these tumours tend to make the eye blind, painful and unsightly. Patients are assessed and staged according with clinical, radiological and pathological criteria from tumour tissue. Despite the advance of eye (and thus sight) preserving treatments such as plaque or proton beam radiotherapy, its devastating prognosis has remained unchanged over the last 30 years. However, when tumour size allows those are preferred in view of the clinical and psychosocial implications of radical surgery. Aims To assess the safety and efficacy of neoadjuvant intravitreous injections of Ranibizumab in high risk ocular melanoma patients. Summary of proposed study Patients with uveal melanoma that require enucleation will enter a two-stage Phase II non-randomised single centre clinical trial. After diagnosis and consent, patients will receive 0.5mg in 0.1ml of intra-vitreal Ranibizumab. Subject to monthly tumour response assessment and provided that tumour progression is excluded treatment will continue 28 days with a second treatment dose. Treatment will continue to a maximum of 6 months doses unless the patient wishes to stop or there is significant toxicity.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/037: STOMP (previously OPIUM-SCLC): A randomised phase II study of olaparib maintenance treatment in patients with chemosensitive small cell lung cancer
Funder: Cancer Research UK

Abstract: A randomised phase II study of olaparib maintenance treatment in patients with chemosensitive small cell lung cancer


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: In situ characterisation of stem cells and their fate in the aging human prostate
Funder: Cancer Research UK

Abstract: BACKGROUND TO THE PROPOSAL: Identification of prostate stem cell markers have been compromised with culture-based approaches leading to deviations from phenotypes observed in vivo. Combined with the previous inability to trace stem cells in situ we do not have a clear understanding of stem cell fate. This is of clinical relevance as abnormal regulation of stem cell fate is thought to be critical to cancer pathogenesis. To overcome these issues, I aim to identify stem cells in situ within benign ageing human prostate tissue. RELEVANCE TO CANCER: Changes in stem cell homeostasis can lead to a proliferative imbalance and is considered a central mechanism to benign prostate hyperplasia and prostate cancer. It is first essential to accurately characterise stem cell processes in the aging prostate before we can reliably establish the critical transforming differences present in cancer stem cells. SPECIFIC AIMS OF THE RESEARCH: - Characterisation of the location and fate of human prostate stem cells in situ - Characterisation of stem cell specific markers and regulatory pathways - In vitro and in vivo study of the identified putative stem cell markers to complete comprehensive functional validation of new stem cell molecular signatures OUTLINE PLAN OF RESEARCH: Mitochondrial DNA (mtDNA) mutations occur within stem cells, and I will characterise the location and fate of human prostate stem cells using 3D gland reconstructions with mitochondrial enzyme-histochemistry and immunohistochemistry. Laser capture microdissection of epithelial stem cell niche will allow comprehensive transcriptome characterisation using RNA microarray analysis. Functional validation of identified stem cell markers will be undertaken using primary culture and xenografts in mice.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CANCER AND NEOPLASMS
Title: Generation of models of renal cell carcinoma by forward genetics
Funder: Cancer Research UK

Abstract: BACKGROUND:_x000D_ Clear cell carcinoma is the most common form of renal cell carcinoma (ccRCC). Despite recent advances in our understanding of RCC biology it remains a difficult tumour to effectively treat. Part of this is a consequence of the limited availability of appropriate genetically defined animal models of the disease._x000D_ _x000D_ RELEVANCE TO CANCER:_x000D_ The development of reproducible and accurate ccRCC mouse models will allow in vivo investigations of the underlying tumour biology and the discovery of new methodologies for the detection, management and treatment of human cancer._x000D_ _x000D_ AIMS OF THE RESEARCH:_x000D_ To establish mouse models of ccRCC using unbiased insertional mutagenesis in renal tubular epithelial cells, thereby identifying genes and pathways involved in ccRCC aetiology._x000D_ _x000D_ PLAN OF RESEARCH:_x000D_ CreERT2 alleles specific for renal tubular epithelial cells will be engineered in embryonic stem cells enabling the direct targeting of conditional mutations in these cells. In adult renal tubular epithelial cells that express inducible creERT2, Sleeping Beauty transposable elements (T2-onc) will be mobilized conditionally from a Rosa26-LSL-SB13 allele following the administration of Tamoxifen. Transgenic mice will be monitored for tumour development. Macroscopically visible primary ccRCC tumours and metastases will be dissected for histological verification, DNA and RNA isolation, and cell lines will be harvested. Linker-mediated PCR will be used to clone transposon integration sites, thereby identifying genes and pathways involved in ccRCC evolution. Novel alleles will be functionally validated to enumerate potential therapeutic avenues for exploration in future studies.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: Identification of tumourigenic pathways and hypoxia induced epigenetic changes in the development of Neuroendocrine Tumours
Funder: Cancer Research UK

Abstract: BACKGROUND AND RELEVANCE TO CANCER:_x000D_ Neuroendocrine tumours (NETs) account for 0.5% of the UK cancer burden. Due to the rarity of NETs and difficulty in obtaining fresh tissue, very little is known about the (epi)genetic changes and gene dysregulation associated with NET development. Integration of genetics and epigenetics has emerged as a powerful approach to study cellular differentiation and tumourigenesis, this approach will be used in this study._x000D_ _x000D_ AIMS AND OBJECTIVES:_x000D_ The aims of the study are (i) the identification and validation of biomarkers relating to the underlying pathology and development of NETs, (ii) assessment of the utility of the identified biomarkers in a cohort of NET patients with metastatic disease (NET01 study) (iii) investigation of hypoxia related (epi)genetic modifications occurring in Von-Hippel Lindau (VHL) competent and deficient model systems_x000D_ _x000D_ OUTLINE PLAN OF RESEARCH:_x000D_ Integrated genome-wide DNA methylation and RNA expression array analysis will be performed on a training set of 200 NET tumour samples and validated on a second set of 200 tumours. This will be performed using Illumina Beadarray technology which allows direct integration of DNA methylation and RNA expression data. Validation of identified biomarkers will then be undertaken in serum derived from a series of NET patients with metastatic disease and matched controls. Epigenetic modifications occurring in hypoxia will be investigated in cell culture based models using VHL competent and incompetent cell lines and a normal pancreatic cell line as a control. The cell lines will be cultured in normoxic and hypoxic conditions and then assessed for global methylation and promoter region specific methylation changes alongside RNA expression analysis and specific histone modifications.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Imperial Cancer Research UK Centre
Funder: Cancer Research UK

Abstract: The Imperial College Cancer Research UK Centre unites the largest NHS trust in the UK with world-class research expertise to tackle cancer. At the heart of the North West London Cancer Network, the Centre is at the forefront of cancer research and patient care. The Centre is a partnership between Cancer Research UK, Imperial College London and Imperial College Healthcare NHS Trust, which has five hospitals in the capital. The Trust is also designated as the UK’s first Academic Health Science Centre, transforming cutting-edge research into benefits for patients as fast as possible. Researchers at the Centre have a particular interest in breast and bowel cancers, and leukaemia. They also specialise in prostate, ovarian and lung cancers, as well as several other types of cancer. Cancer surgery is a high priority at Imperial College, and doctors here are leading the world in developing robotic and keyhole surgery. Researchers at the Centre are also using state-of-the-art technology to develop and test the latest radiotherapy and laser therapy techniques. Another area of expertise is cancer imaging. Scientists at the Centre are developing more accurate ways to track the growth and spread of the disease within the body, and to see how well treatment is working. Imperial also has great strengths in the area of cancer biology, and developing and testing new cancer drugs. Research at the Centre will reveal more about how to treat cancer on an individual level, helping doctors to select the most appropriate treatment based on the genetic makeup of a person’s tumour. The Imperial College Cancer Research UK Centre also includes the St Mark’s Family Cancer Group, which is investigating the causes and prevention of bowel cancer. Researchers at the Centre are also investigating more effective screening techniques, to help doctors diagnose bowel cancer earlier and save lives. Finally, Imperial College is a world-famous medical school, attracting some of the brightest and best scientists and doctors from around the world. The Centre will provide a fertile environment for training the cancer workforce of the future, bringing benefits to patients now and for years to come


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: El-CID: Improved Lung Cancer Identification by targeted chest X-ray
Funder: Cancer Research UK

Abstract: Lung cancer is one of the commonest cancers in the UK, and five-year survival in the UK is just over 5%, compared with 13% in the US and similar proportions for other EU countries. Compared with other countries, the UK has more advanced stage at presentation, a low rate of lung cancer resections, and poorer survival. In order to improve survival figures in the UK, a greater proportion of resectable cancers must be diagnosed. Apart from screening, currently of unproven benefit, the only way of achieving this is to reduce the time from symptoms to diagnosis. Currently, lung cancers are mainly diagnosed by GPs referring patients for CXR. NICE guidance recommends urgent referrals for patients who have one of a number of chest symptoms for more than 3 weeks. Based on evidence from GP databases, we are proposing to expand this recommendation (‘extra-NICE’) to include one of a number of chest symptoms of any duration in patients who smoke and are over 60 years of age i.e. high risk patients. This proposal is to investigate whether or not it is feasible to run a full trial to answer the question: does an urgent chest x-ray (CXR) for patients with potential lung cancer symptoms, not currently included in the NICE guidance, improve survival and is this cost effective and acceptable to patients and GPs? The study will: 1.conduct workshops with GPs and patients to ascertain:- a. the feasibility of GPs to recruiting and randomising patients to an urgent CXR (or not) b. the best way to train GPs to identify and recruit patients c. the best way of presenting the trial (and randomisation) to patients 2. conduct a pilot trial: select patients who fulfil ‘extra-NICE’ (and not NICE) criteria from between 20 - 30 general practices over 6 months. They will be individually randomised to receive an urgent CXR or ‘watchful waiting’. Qualitative interviews will be conducted with patients and GPs. This pilot will ascertain: a. the prevalence of ‘extra-NICE’ symptoms in patients visiting general practices, the proportion of those that will be diagnosed with lung cancer and the best sources of routine data b. the barriers to recruitment and how can we overcome them c. the best tools to use to measure anxiety/depression that may be caused by unnecessary CXRs/no CXRs d. the best measures of resource use to facilitate health economic analysis of the cost-effectiveness of ‘extra-NICE’


Research activity codes: 4.3 INFLUENCES AND IMPACT;7.3 MANAGEMENT AND DECISION MAKING;8.2 HEALTH AND WELFARE ECONOMICS;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Research into chronic B cell lymphoproliferative disorders
Funder: Cancer Research UK

Abstract: Our long term aim has been to identify and evaluate both clinical and biomarkers in chronic lymphocytic leukaemia (CLL) and other chronic lymphoprolferative disorders, especially splenic marginal zone lymphoma(SMZL). In conjunction with our collaborators we are involved in the following projects. 1) Identifying novel genes on chromosome 13q in CLL and 7q in SMZL of importance in the pathogenesis in these disorders. 2) Determining the optimal assay(s) for detecting loss and/or mutation of the TP53 gene and 11q loss / ATM mutations in CLL 3) Evaluating the prognostic value of a panel of biomarkers including genomic abnormalities, IGHV gene mutational analysis, expression of CD38, CD49d and ZAP70 and telomere length in CLL patients either at diagnosis or prior to treatment. The expectation is that these studies will continue to provide clinically useful information on the natural history of these disorders and help to determine the choice of therapies.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: ColoRectal Early Diagnosis: Information Based Local Evaluation (CREDIBLE)
Funder: Cancer Research UK

Abstract: Background and relevance Existing software can be adapted to automatically identify patients from electronic primary care records who meet NICE criteria for investigation of suspected colorectal cancer. The lead applicant has pioneered the use of a similar approach to identify, invite, assess and treat patients at high risk of cardiovascular disease. As a result he has established relationships with the PCT, general practices and software company which are needed to implement early identification of suspected colorectal cancer. Electronic records indicate that about 40% of patients with colorectal cancer met NICE referral criteria on average 5 months before diagnosis. Reducing this delay may reduce the number of cases that present as emergencies and therefore improve outcome. Identifying symptomatic colorectal cancer complements screening for asymptomatic cancer. Aims Following the MRC framework on complex interventions, before evaluating electronic identification in a RCT, we should investigate feasibility and acceptability. This project is a feasibility study of early identification of suspected colorectal cancer in primary care. Plan of research By adapting MSDi software already in place in Sandwell PCT we will prospectively identify patients eligible for referral over an 18 month period from a population of 20,000 aged 60 to 79 (about 20 practices). We will determine the numbers in whom referral is indicated (not already under investigation, no existing explanatory diagnosis, have not refused investigation). We will offer referral to a specialist service for those eligible and without contraindications and determine the numbers who are referred. We will determine the main diagnostic outcomes in identified patients. We will also investigate the extent to which this complements early diagnosis through bowel cancer screening. Applying NICE referral criteria to our population of 20,000 adults we expect to identify 1007 patients eligible for referral (3 per month per practice) of whom 25 will have colorectal cancer. Up to 3 times this number may have polyps. We will determine the numbers of new referrals generated, numbers assessed and final diagnoses. We will determine if this identifies different cancers to those identified by screening. We will explore the potential of an alternative score (CAPER) for identification of colorectal cancer patients. Nested within this we will conduct qualitative research into the acceptability of the process to primary care staff and to patients. Interviews and focus groups will be conducted with primary care staff, patients participating in the process and patients who do not / partly participate.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: An investigation into the cognitive factors for missing early presentations of cancer in primary care.
Funder: Cancer Research UK

Abstract: Background: In a recent study, we investigated the cognitive causes of diagnostic error in General Practice, using carefully developed, realistic (non-cancer) patient scenarios presented on computer to GPs. Diagnoses were missed usually because they were never considered. Symptoms and signs were attributed to a more prevalent, competing diagnosis, while important clinical information was not checked, ignored or explained away. We also found that the working diagnosis influenced the way clinical information was interpreted: the same symptom in a patient could be seen differently by GPs with different working diagnoses. Relevance: Given that early presentations of cancer are characterised by ‘soft’ symptoms rather than red flags, it is important to know how GPs deal with such symptoms and whether cancer is ever considered as a possibility. We propose to carry out a similar investigation into GPs’ cognitive processes during cancer diagnosis. A greater understanding of the processes involved will help inform countermeasures. Aims: To understand better the reasons that early presentations of cancer may be missed by GPs. Specifically, to investigate whether this is due to not considering cancer as a diagnostic possibility or not appreciating the diagnostic significance of certain symptoms and signs. Plan: All GPs from Lambeth, Southwark and Lewisham PCTs will be invited to participate and 79 will be recruited randomly from the volunteers (sample size calculated on the basis of a logistic regression power analysis). We will develop a number of patient scenarios, with cancer as a differential diagnosis. We will review the literature to identify the evidence underlying the presenting symptoms and signs. Scenarios will include both diagnostic and non-diagnostic information. For each scenario, we will determine the most appropriate differential diagnoses and management. We will present the scenarios on computer to GPs and record the information that they request, their diagnostic hypotheses, and their final diagnoses and management decisions. In some scenarios, we will also collect concurrent verbal protocols, to identify how GPs interpret the information elicited in relation to their diagnostic hypotheses. We will perform logistic regressions to identify predictors of diagnostic accuracy and appropriateness of management. A number of predictor variables will be tested, including the number and timing of diagnostic hypotheses, time taken, and number and type of information requested by participants. The verbal protocols will be used to identify the way clinical information is interpreted and assess this against the published evidence. We will thus establish what clinical features are consistently misinterpreted.


Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS