NIHRDataInsights/HRCSData huggingface dataset:
Title: Symposium to celebrate the Royal Society of Chemistry 2014 George and Christine Sosnovsky Award in Cancer Therapy to Professor Roger J Griffin, Newcastle University
Funder: Cancer Research UK

Abstract: Symposium to celebrate the Royal Society of Chemistry 2014 George and Christine Sosnovsky Award in Cancer Therapy to Professor Roger J Griffin, Newcastle University


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: A Week In Your Life
Funder: Cancer Research UK

Abstract: Background Previous research has demonstrated that teenage mothers are at higher risk of engaging in cancer-causing behaviours such as smoking, poor diet and lack of physical activity. Most research in the area of teenage mothers and health has focused on the health of children born to teenage mothers rather than the health behaviours of the mothers themselves. To develop interventions aimed at changing teenage mothers’ health behaviours, researchers need to understand the everyday lived experiences of this harder to reach group. Aims The aim of this research is to create a rich qualitative evidence base through which an intervention to address teenage mothers’ risky health behaviours could be developed. Through this evidence base we will; (i) Understand the everyday lives of teenage mothers from their own perspective; (ii) Identify the barriers to, and facilitators of, good health behaviours in this population;(iii) Produce a framework through which an intervention to address risky health behaviours in this population can be developed, Methods Our sample will be approximately 60 teenage mothers (up to 19 years old) from three areas of the UK; Middlesbrough, Bristol and Belfast (20 in each area). We will recruit participants through Sure Start Centres and/or other relevant bodies. We will use photo elicitation and focus groups to understand the everyday lives of teenage mothers. Participants will be provided with disposable cameras and asked to take photographs documenting a typical week in their life. Following this, two rounds of focus groups will be undertaken which will (i) discuss the meanings of these photographs, (ii) identify the key features of teenage mothers’ everyday lives with a focus on their health choices/behaviours and (iii) work collaboratively with the participants to develop and refine a framework which could inform an intervention that aims to improve cancer-preventative behaviours in teenage mothers How the results of this research will be used. The results will be used as an evidence base through which to develop an intervention that is specifically targeted at teenage mothers as a harder to reach population who are known to engage in risky health behaviours. We intend to apply for feasibility funding to test this intervention, which would aim to improve cancer-preventative behaviours. The methodological tool we develop in this research can also be used to understand the everyday lives of other harder to reach groups, thus improving cancer prevention in a wider population.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Equipment supplement: The role of SOX and FOX genes in orchestrating transcriptional and epigenetic programs in glioblastoma
Funder: Cancer Research UK

Abstract: Glioblastoma (GBM) is one of the most devastating human cancers. There are few treatment options and median survival is only around one year. Sequence-specific transcription factors required for normal neural stem cell self-renewal are likely to play critical roles in driving unconstrained self-renewal in GBM. Particularly interesting are members of the forkhead box (FOX) and SRY-related (SOX) families, which orchestrate lineage choice, differentiation and proliferation/survival pathways in the developing nervous system. For example, there is clear evidence that FOXG1 and SOX2 cooperate to establish and sustain the neural stem cell state. Although each of these factors has been previously implicated in human GBM, we have poor mechanistic understanding of their specific functions and key downstream effectors. Aims: We will define the specific function, molecular partners and transcriptional targets of FOXG1 and SOX2 in normal human neural stem (NS) cells and GBM-derived neural stem (GNS) cells. Our hypothesis is that in GBM the increased level and/or activity of these factors restricts differentiation, locking cells into a continuous cycle of self-renewal. There are three complementary aims: 1) Test the role of SOX and FOX in establishing and sustaining GBM. 2) Determine the molecular basis of SOX2 and FOXG1 activity by defining their molecular partners and key transcriptional targets. 3) Exploit our expertise in genome editing to explore FOX and SOX gene function and create live cell reporters for drug screening. Methods: We will use primary human GBM-derived cell lines as a tractable and disease-relevant model. We have routine access to fresh tumours and a set of well-characterized GNS cell lines. Intracranial transplantation will be used to assess the malignancy of cells following perturbation of FOXG1 and SOX2. Tumour initiation will be tested by delivery of lentiviral overexpression vectors into the mouse forebrain. ChIP-seq, and immunoprecipitation mass spectometry (IP-MS) will be used to determine targets and partners, respectively. Genome editing methods (TALENs and/or CRISPR/Cas system) will be exploited to generate conditional alleles and knock-in reporters. How the results will be used: SOX2 and FOXG1 proteins are important therapeutic targets, yet we need to define their precise molecular activities to identify ‘druggable’ effectors. These might be direct protein partners within the transcriptional/chromatin regulatory complex, or downstream transcriptional targets. The SOX2 and FOXG1 reporter cell lines developed in this project will be of immense value for cell based screening for new drug discovery.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Star Scientist Award - Transitional Support for new team leader
Funder: Cancer Research UK

Abstract: The laboratory comprises a broad spectrum of programs in small RNA biology, mammalian genetics and genomics. We study RNAi and related pathways in a wide variety of organisms to extract common themes that define both the mechanisms by which small RNAs act and the biological processes which they impact.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/06/019: STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy. A three-stage multi-arm, randomised controlled trial
Funder: Cancer Research UK

Abstract: Background: <br />Prostate cancer (PCa) is the second commonest cancer In UK men. Metastatic disease IS treated by androgen suppression (AS). Most patients respond. but disease usually recurs (median 18-24 months). Some systemic agents used at recurrence produce prostate-specific antigen response and symptom palliation, but do not influence survival. <br /><br />Objective: <br />To determine whether addition of systemic agents to standard AS as first-Iine treatment prolongs failure-free survival (FFS) and overall survival (OS) in patients with locally advanced or newly diagnosed metastatic PCa. <br /><br />Design:<br /> Three-stage, multi-arm, randomised controlled trial. In the Pilot phase and Stage 1, eligible consenting patients will be randomised between: <br />Arm A: Androgen suppression (AS) based on LHRH analogue (Control). <br />Arm B: AS + Bisphosphonate (zoledronic acid). <br />Arm C: AS + Chemotherapy (docetaxel + prednisolone). <br />Arm D: AS + COX-2 inhibitor (celecoxib). <br />Arm E: AS + Bisphosphonate + Chemotherapy <br />Arm F: AS + Bisphosphonate + COX-2. <br /><br />Arms that improve failure-free survival (FFS) in Stage 1 analyses will be considered for comparison in Stage 2, where OS and quality of life (QL) will be the main outcome measures. <br /><br />Application: <br />The outcome for these patients is poor at present. There is little evidence that current therapeutic options improve survival. Several second-line treatments are available, but little evidence shows whether any of them have a role in first-Iine treatment. This 3-stage multi-arm design will permit rapid comparison and testing of the main treatment options that are currently available. Agents that improve survival or OL would substantially impact practice in advanced PCa worldwide. Last updated 01/08/2010


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/05/002: BILCAP: Biliary tract cancer treatment with capecitabine
Funder: Cancer Research UK

Abstract: Biliary tract cancer (BTC) is becoming more common with cholangiocarcinoma increasing 10 fold over the last ten years. The majority of patient present with advanced disease and of those that proceed to potentially curative resection, the majority relapse and the only randomised trail in this area reports a 2-year survival of 20%. Oncologists in the UK commonly do not give adjuvant chemotherapy in post portative BTC patients, even though the condition may be chemo-sensitive. However, in the USA, chemotherapy is often given in spite of the lack of an evidence base for its use. The only phase 3 trial looking at adjuvant chemotherapy in BTC revealed a significant survival benefit using a combination of fluoropyrimidine combined with mitomycin C in patient with gall bladder cancer, but the trial was underpowered to show this in cholangiacarcinoma and no survival advantage was reported with BTC overall. Therefore, there is a need to evaluate the efficacy of adjuvant chemotherapy in an adequately powered prospective, randomised clinical trial. BILCAP has been endorsed by the NCRI Upper GI Clinical Studies Group and aims to establish the efficacy of adjuvant chemotherapy with oral 5-FU (capecitabine) in terms of survival, progression free of survival toxicity.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: ASPECT: aspirin/esomeprazole chemoprevention trial
Funder: Cancer Research UK

Abstract: In the UK oesophageal adenocarcinoma causes over 5% of cancer related mortality and yet it has only 1.4% of the NCRI budget spent on it. Prevention of cancer is a vital strand of the national plans for the NHS yet only 2% of the NCRI budget is spent on this compared with 9% in the NCI USA. This is one of the World's largest upper GI chemoprevention trials and aims primarily to prevent conversion to cancer in patients with the pre-malignant lesion, Barrett's metaplasia. The interventions evaluated are high versus standard dose proton pump inhibitor therapy and aspirin versus no aspirin. We will also assess whether aspirin reduces all cause mortality. Our trial provides useful secondary outcomes exploiting a unique collection of thousands of patients with combined serial tissue and blood samples together with detailed clinico-pathological information. Our trial represents a real opportunity for the UK to grasp the initiative and produce robust generalisable data for the management and improved understanding of oesophageal adenocarcinoma. Our trial will also represent a net saving to the NHS as all the patients enrolled would have been taking lacid suppression medication and now this will be provided free to a net saving of £15,000,000.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: IBIS II
Funder: Cancer Research UK

Abstract: IBIS II is a randomised double-blind controlled trial divided into two strata. The prevention study will compare anascrozole vs placebo in high risk women without cancer and the DCIS study will compare tamoxifen vs anastrozole in women with locally-excised oestrogen receptor positive ductal carcinoma in situ (DCIS). IBIS II - Prevention In post-menopausal women, oestrogen is only produced in a adipose tissue by the aromatization of androgens. Aromatase inhibitors have been shown to be more effective in treating oestrogen receptor positive than tamoxifen and are particularly effective at preventing new contralateral tumours in this adjuvant setting. Anastrozole is the most fully studied of these compounds and has also shown a very favourable side effect profile. In this trial, anastrozole or placebo will be given to 6000 postmenopauaal women who are at a 'high risk' of developing breast cancer or a randomised basis. Tamoxifen or anastrozole in post-menopausal women with DC1S of the breast (IBIS II - DCIS) ductal carcinoma in situ (DCIS) means that the cells inside the ducts of the breast have started to turn into cancer cells. Oestrogen positive DCIS responds to hormonal treatment in a manner similar to invasive breast cancer. This trial will compare anastrozole to tamoxifen in 4000 women with locally excised receptor positive DCIS.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/004: BOXIT: A Randomised phase III placebo-controlled trial evaluating the addition of celecoxib to standard treatment of transitional cell carcinoma of the bladder
Funder: Cancer Research UK

Abstract: 11,000 cases of bladder cancer are diagnosed in the UK each year. 70% are superficial tumours. lntravesical BCG immunotherapy and Mitomycin-C (MMC) chemotherapy are standard adjuvant treatment for UK patients with high or intermediate risk transitional cell carcinoma (TCC) of the bladder. Despite benefit, up to 40% of tumours recur and ultimately progress to invasive bladder cancer. BCG and MMC result in local and systemic side effects including cystitis and polyarthritis. Epidemiological studies have confirmed the potential importance of COX-2 inhibition in bladder cancer patients. Pre-clinical studies demonstrate that inducible COX-2 is overexpressed in bladder cancer but not normal urothelium and expression increases with grade and stage. Selective COX-2 inhibition has been shown to reduce growth of human bladder cancer in vitro by apoptotic mechanisms and suppresses tumourigenesis in animal models in vivo. BOXIT tests the hypothesis that inhibition of the COX-2 enzyme reduces recurrence of TCC of the bladder. 1760 patients will be recruited to a phase 3 multi-centre double-blind placebo-controlled raridomised trial. The primary endpoint is recurrence-free survival. A subset of centres will participate in a substudy to determine if celecoxib improves quality of life and reduces inflammatory side effects associated with MMC and BCG therapy.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CHOPIN: chemoprevention of premalignant intestinal neoplasia
Funder: Cancer Research UK

Abstract: The CHOPIN trial aims to support the ASPECT trial which is the largest upper gastrointestinal chemoprevention trial in the world. The CHOPIN trial aims to validate putative biomarkers recommended by the NCI. The current application aims to address biomarkers and genome wide analysis of single nucleotide polymorphisms The samples will be processed centrally and distributed as appropriate to known centres (mostly CRUK) for immunocytochemistry, flow cytometry, genotyping, LOH, mutational and methylation and methylation analysis. In the second phase genome wide SNP analysis will be conducted in certain high risk lesions in order to identify allelic changes involved in disease progression and response to therapy as well as allowing a detailed insight into both clonality and field changes in Barretts Metaplasia. To date we have in excess of 1,500 samples and this represents the largest Barretts prospective collection in the world. Furthermore we have collected many control samples from related populations so association and genetic linkage studies are also in the advanced planning stage.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: CRUK/06/027: ESSG1 - European Paediatric Soft Tissue Sarcoma Study Group
Funder: Cancer Research UK

Abstract: This study of non metastatic rhabdomyosarcoma in children and young people is proposed through the recent collaboration of three European paediatric soft tissue sarcoma co-operative groups. It is the first pan European study for this group of patients the proposed treatment is based on a new risk stratification using pathology (alveolar versus non alveolar), post surgical stage, site, presence of local lumph node, size of tumour and patients age. The objectives of the study are; 1) For patients stratified in low, standard and very high risk groups to give homogenous local and systemic treatment (observational study). 2) for those stratified as high risk to evaluate a) the role of Doxorubicin given in dose intensity early in treatment and b) the role of maintenance chemotherapy with Vinorelbine and Cyclophosphamide (phase III randomized, open study). The primary end point is event free survival. Secondary end points are overall survival, progression free survival, response rate and toxicity. Patients in the UK will be recruited through the existing network of the Children's Cancer and Leukaemia Group. It is anticipated that 200 patients will be recuited over a five year period in the UK.


Research activity codes: 6.4 SURGERY;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CTSU Liquid Nitrogen Blood Storage Facility (jointly funded with the MRC and the BHF)
Funder: Cancer Research UK

Abstract: Liquid Nitrogen Blood Storage Facility linked to the Clinical Trials Service Unit. The work of the CTSU chiefly involves studies of and treatment of cancer and other major chronic diseases (such as heart attack and stroke).


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/06/025: ST03: A randomised phase II/III study of peri-operative chemotherapy with or without bevacizumab in patients with operable adenocarcinoma of the stomach and gastro-oesophageal junction
Funder: Cancer Research UK

Abstract: Background: Surgery is the only curative treatment for gastric carcinoma but 5 year survival rates with surgery alone remain poor at around 20%. The MRC ST02 trial has shown that peri-operative chemotherapy with epirubicin, cisplatin and 5-fluorouracil improves overall survival: 5 year survival rates increased from 23% in the surgery alone arm to 36% in the combined arm, hazard ratio 0.75 (95% CI: 0.60, 0.93), p=0.009. Bevacizumab is an anti-vascular endothelial growth factor monoclonal antibody. The addition of bevacizumab to chemotherapy in patients with advanced colorectal cancer has been shown to improve survival. Early data suggests that the addition of bevacizumab to chemotherapy in advanced gastric carcinoma also improves outcomes. Aims and Outline of the Research: This 2-stage randomised controlled trial is designed to investigate whether the addition of bevacizumab to peri-operative chemotherapy improves survival of patients with operable gastric and gastro-oesophageal tumours. In the first stage the safety and feasibility of combining bevacizumab with peri-operative chemotherapy in this group of patients will be confirmed. The aim of the second stage is to assess the effects of the combined treatment on overall survival, disease free survival, response rates to pre-operative treatment, surgical complete resection rates, treatment-related morbidity, cost-effectiveness and quality of life.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: SPARE: Feasibility study for a randomised trial of Selective bladder Preservation Against Radical Excision (cystectomy) in muscle invasive T2/T3 transitional cell carcinoma of the bladder
Funder: Cancer Research UK

Abstract: SPARE is a randomised trial of Selective bladder Preservation Against Radical Excision (cystectomy) in muscle invasive transitional cell carcinoma of the bladder. SPARE compares the standard treatment of muscle invasive bladder cancer which is surgical removal of the bladder (cystectomy), with the new approach of selective bladder preservation. Selective bladder preservation uses the patient’s response to neo-adjuvant chemotherapy to assess their suitability for treatment with radiotherapy. If the patient’s cancer is found to respond to three cycles of chemotherapy, they will proceed to a further cycle and then receive radical radiotherapy. If the patient’s cancer does not respond sufficiently they will proceed directly to surgery. SPARE is randomising participants between cystectomy and selective bladder preservation. There is an initial feasibility stage to assess patient acceptability of the trial. The target sample size for the feasibility study is 110 participants, the main trial aims to recruit 1,015 participants in total. There are a number of sub-studies associated with the main SPARE trial. The qualitative, or interview, study aims to evaluate patient response to trial information. A new qualitative sub-study has recently been initiated to examine communication between health professionals and people with invasive bladder cancer. The quality of life study will assess the impact of the randomised treatments on participants’ physical, emotional and social wellbeing. The biological samples study will examine tissue samples from surgical and biopsy specimens to investigate the biological mechanisms behind bladder cancer. (http://www.icr.ac.uk/our-research/our-research-centres/clinical-trials-and-statistics-unit/clinical-trials/spare)


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/001: QUARTZ - A phase III multicentre randomised trial to assess dexamethasone +/- whole brain radiotherapy in patients with inoperable brain metastases from non-small cell lung cancer
Funder: Cancer Research UK

Abstract: Cerebral metastases, from any primary, are a devastating occurrence and most patients deteriorate quickly over a matter of weeks. A number of treatment options have been investigated, but for many years, the standard therapy for patients with inoperable brain metastases has remained a combination of steroids and Whole Brain Radiotherapy (WBRT). However, WBRT can be toxic and has not been shown to consistently improve length or quality of survival, particularly for patients with a non-small cell lung cancer primary The aim of this trial is to determine whether dexamethasone alone is as effective as dexamethasone plus WBRT in terms of overall quality of survival time for patients with inoperable brain metastases originating from non-small cell lung cancer, when both groups of patients are also receiving optimal supportive care At the time of referral to the oncology centre, the vast majority of patients will be receiving optimal supportive care (OSC) including dexamethasone for symptom relief. Patients will continue to receive this treatment and in addition will be allocated WBRT (20 Gy in 5 consecutive daily fractions) or not. Because these patients have a short survival time, and may not be well enough to be seen in clinic; a nurse will assess all patients via a weekly telephone call.


Research activity codes: 6.4 SURGERY;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS