NIHRDataInsights/HRCSData huggingface dataset:
Title: Exploring reasons for non-attendance at colonoscopy among socioeconomically deprived South Asian, Eastern European, Southern European and White British adults taking part in the new faecal immunochemical test (FIT) bowel screening programme
Funder: Cancer Research UK

Abstract: Background: Bowel cancer is a leading cause of mortality in England. Several large randomised controlled trials have shown that biennial guaiac faecal occult blood test (gFOBt) screening can reduce deaths by detecting cases early. In light of this, NHS England initiated a national bowel cancer screening programme (BCSP) in 2006. Since then, uptake of the test has been consistently low, falling from 54% in 2010, to 49% in 2014. It is believed that, when the English BCSP transitions to a new test, called: the ‘faecal immunochemical test’ (FIT), participation will increase, as the new test has been shown to be more acceptable. This will lead to a concomitant increase in the number of people with abnormal test results invited for follow-up diagnostic testing (usually via colonoscopy). Recent evidence from the English BCSP and FIT pilot suggests that ~15% of FIT-positive adults do not attend their follow-up colonoscopy, and that attendance is lowest in the most socioeconomically deprived and ethnically diverse areas. Aims: The present research aims to identify and address factors associated with non-attendance in areas with low follow-up colonoscopy attendance. The primary objectives are to: i) use the Theoretical Domains Framework (TDF) to identify factors underpinning non-attendance at follow-up colonoscopy among socioeconomically deprived and ethnically diverse areas, and ii) apply the Behaviour Change Wheel (BCW) to design and test the effectiveness of behavioural interventions to address individual targets. Methods: Focus groups with patients and specialist screening practitioners will be conducted to explore barriers to colonoscopy among individuals who live in socioeconomically deprived and ethnically diverse areas with low follow-up colonoscopy attendance. Video observations of the pre-colonoscopy assessment, which precedes follow-up colonoscopy, will also be performed to examine verbal and non-verbal factors affecting follow-up attendance in centres with demographically similar populations and pre-colonoscopy attendance, but either high or low attendance at follow-up. The data from these studies will be analysed using thematic analysis, with themes mapped onto the TDF. The BCW will then be used to identify candidate BCTs to modify relevant domains. Candidate BCTs will subsequently be tested in a series of online experiments, with those that prove to be effective selected for inclusion in prospective interventions, which will be developed through co-design workshops. How the results will be used: The findings will result in clear recommendations for the design of follow-up colonoscopy communication and thereby improve the effectiveness of the English BCSP to reduce deaths from bowel cancer.


Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: CANCER AND NEOPLASMS
Title: CRUK/11/043: De-ESCALaTE COLLECT - Head and neck squamous cell carcinoma Tissue Collection for the De-ESCALaTE trial (De-ESCALaTE COLLECT)
Funder: Cancer Research UK

Abstract: De-ESCALaTE-HPV is the first biomarker-driven head and neck study to be run in the UK and one of the first in the world. Background Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing rapidly in the developed world. This rise has been attributed to Human Papillomavirus (HPV) infection. HPV+ve OPSCC is a distinct disease, which affects younger patients and has a good prognosis, meaning patients will live with the considerable side effects of treatment for several decades. Radiotherapy and Cetuximab (Epidermal Growth Factor Receptor-inhibitor) demonstrated similar efficacy to platin chemoradiotherapy (current standard treatment) in head neck cancer, but is potentially less toxic. Aims and Relevance to Cancer For HPV+ve OPSCC, compared to current standard, will cetuximab + radiotherapy result in: 1. Less morbidity (late and acute toxicity)? 2. Better quality of life? 3. Better cost effectiveness? 4. To compare toxicity of CRT between HPV+ve and HPV-ve OPSCC? Outline plan Using standardised protocols, diagnostic tissue blocks and 40ml-blood and oral rinse fluid will be collected at pre-treatment, 3 months and 1 year after treatment, and at recurrence, and neck dissection blocks if appropriate. In total, we aim to collect 1,050 blood samples, 1,050 oral rinse samples and 1,750 tissue blocks. Samples will be bio-banked in HBRC, a dedicated state-of-the-art tissue banking facility for use in future studies. MREC and MHRA approval for trial and tissue collection already secured. 14 HNC centres in UK are currently in set-up, 5 have started recruiting with 2 patients already recruited.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: TWEET: A randomised phase II Trial of WEE1 inhibitor (AZD1775) with Taxane chemotherapy (paclitaxel) versus paclitaxel in head and neck squamous cell carcinoma
Funder: Cancer Research UK

Abstract: Background Patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) have a poor prognosis after relapse or progression on previous platinum-based chemotherapy. Nivolumab has been shown to increase survival in these patients but only a small proportion of these patients respond to this treatment. There remains a need to find ways that can improve the outcome for these patients. P53 is a key regulator of the G1/S checkpoint of the cell cycle. In HNSCC, there is a high frequency of TP53 mutations, which could impair the function of G1/S checkpoint resulting in the cancer cells reliance on the later G2/M checkpoint. WEE1 inhibition could lead to the cell progressing through the G2/M checkpoint without repairing DNA damage and thus generates potentially mitotic catastrophe, leading to cell death. In addition, Wee1 kinase is required for normal entry into and exit from mitosis. WEE1 inhibitor promotes cancer cells to bypass the cell-cycle checkpoints and prematurely enter mitosis as well as delays mitotic exit, resulting in mitotic arrest. The addition of WEE1 inhibitor to paclitaxel increased total time in mitosis and can sensitize cancer cells to paclitaxel treatment, providing a rationale of combining paclitaxel with WEE1 inhibitor We hypothesize that WEE1 inhibition would enhance treatment response and clinical benefit of single agent paclitaxel in HNSCC patients who have had previous platinum-based chemotherapy. Aims The overall aim of the randomized phase II study is to assess whether there would be an improvement in progression-free survival (PFS) and other efficacy outcomes including overall survival (OS) in these patients treated with paclitaxel + AZD1775 compared with paclitaxel alone. Methods We propose a randomised phase II study of AZD1775 in combination with paclitaxel in patients with HNSCC who have had previous platinum-based chemotherapy. We will include 42 patients in each arm (paclitaxel + AZD1775 versus paclitaxel alone). How the results of this research will be used The success criterion for further development of this combination would be a demonstration of a statistically significant increase in PFS. This study could be developed into an adaptive phase II/III trial with PFS as an intermediate outcome and OS as definitive outcome. If there was sufficient evidence from the biomarker aspect of this study, then a new proposed phase III study could be done and would consider the use of a biomarker enrichment design, which would incorporate early stopping rules for futility in the enriched population.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: NEED-2: Non-invasive Testing for Early oEsophageal Cancer and Dysplasia
Funder: Guts UK

Abstract: Background: Early oesophagogastric cancer typically has non-specific symptoms that could be wrongly attributed to common benign conditions while red-flag symptoms are often associated with advanced disease. The primary investigation to detect oesophagogastric cancer is endoscopy, which is invasive, expensive and consumes NHS resources. It is not feasible to refer all patients with upper gastrointestinal symptoms to have endoscopy. Because of late diagnosis, five-year survival for oesophagogastric cancer in the UK remains between 15-20%. The key to improving survival is earlier detection. Breath testing has the ideal characteristics for a triage test as it is non-invasive and acceptable to patients. In NEED-1 study we developed a model for VOC analysis in 250 patients using advanced two-dimensional Gas-Chromatography-Time-Of-Flight-Mass-Spectrometry (GC-TOF-MS) with an area under the receiver operator characteristic curve (AU-ROC) of 0.91 to detect T1 oesophageal adenocarcinoma and high-grade Barrett’s dysplasia. Hypothesis and aims: The hypothesis is that breath testing can accurately predict early oesophageal cancer (T1) and high-grade Barrett’s dysplasia. The primary aim is to validate a non-invasive breath test to detect early oesophageal cancer and high-grade dysplasia and to determine its sensitivity and specificity. Design and population: Double-blind diagnostic multicentre independent validation study where both the VOC analyst in the laboratory and the person classifying the VOC profile into cancer/no-cancer will be unaware of disease status. 144 patients will be recruited from endoscopy lists for resection of early oesophageal cancer lesions and/or high-grade dysplasia and for ablation of Barrett’s oesophagus. 144 control patients will be recruited from endoscopy lists for Barrett’s surveillance and two-week-wait referral pathway. Twelve centres will be invited to participate in NEED-2. The reference standard test is oesophago-gastro-duodenoscopy ± histopathology. Plan of investigation: All breath samples will be retrieved prior to the planned procedure. Patients will exhale in a single use 2L polytetrafluoroethylene (PTFE) breath bag and a breath sampling device will pump breath from the sample bag across two thermal desorption (TD) tubes at a rate of 200ml/minute. TD tubes contain Tenax/Carbograph-5TD sorbent and are made of stainless steel (89mm long, 64mm outer diameter) allowing robust transport and no significant VOC loss for up to three months (at -800 C). GC-TOF-MS will be used for VOC analysis. To assess diagnostic accuracy in thisindependent validation study, a positive test will be defined if model prediction of early oesophageal cancer and high-grade dysplasia exceeds a predefined threshold. The impact on endoscopy services will be estimated as the number of false positive or incomplete tests, as well as the number of endoscopies that could be prevented (true positives).


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/15/006: BIOMEDE - Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication (jointly funded by The Brain Tumour Charity)
Funder: Cancer Research UK

Abstract: Background: Diffuse Intrinsic Pontine Gliomas (DIPG) is a childhood brain tumour, with ~30 new cases/ year in UK. Their clinical presentation is stereotypical with a short clinical history and a unique MRI appearance usually considered as sufficient to establish the diagnosis. The prognosis of DIPG is dismal; median overall survival is 9 to 10 months and most patients will die within two years. DIPG represent the greatest challenge of paediatric oncology; despite numerous collaborative studies performed, patients’ survival has not significantly increased in thirty years. There is currently no validated treatment except radiotherapy which is essentially palliative. New therapies have been evaluated one after the other in search of a treatment that would be effective for all patients and they have all rejected as ineffective. However it maybe that sub-groups of patients based on underlying biology may benefit from a specific targeted therapy. We need a different trial design to link biology to therapy and survival. Routine biopsy has not been used in classical DIPG but recent data has confirmed the safety of this in children and indeed has helped to provide tissue that has undergone genomic analysis revealing the unique biology of DIPG compared to other malignant gliomas in adults and children. It also appears that there are different molecular sub-types of DIPG which expresses differing potential therapeutic targets. Aim: to mandate biopsy of DIPG in a clinical trial setting and enrich the allocation of treatment in each patient to increase the likelihood of activity, based on the specific biological tumour profile. Methods: An International, adaptive designed (possibility of introducing new therapeutic arms as novel targets and agents emerge), randomised, open-label phase II trial designed to recruit 150 patients with DIPG over 4 years. The initial agents to be studied based on biomarkers profile are; Dasatinib, Erlotinib and Everolimus as single agents combined with standard irradiation. How will the results of the trial be used: The results will be published in peer reviewed journals and will inform best clinical practice for children with DIPG. Requests for data sharing will be reviewed by the TSC to ensure they are scientifically appropriate. The appropriate regulatory and ethical requirements will be adhered to when data sharing.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: BTC-VBT: Biliary Tract Cancer Studies translational material bank (supported by Stand Up To Cancer)
Funder: Cancer Research UK

Abstract: Background There are approximately 1500 cases of BTC in the UK every year and mortality rates have risen steeply and steadily over the past 30 years. Surgery is currently the only curative treatment but is only possible in approximately 20% of cases and reported 5-year survival rates vary from 9-30%. The remaining 80% of cases require palliation of symptoms and treatment with other modalities. The UK has proven itself to be at the forefront of BTC clinical research. The BILCAP study has investigated the value of adjuvant capecitabine in resected disease and completed accrual in autumn 2014. The ABC-02 study established cisplatin + gemcitabine as the standard of care for advanced and metastatic disease (ABC). Since then, a series of trials have been undertaken or are in set up in the adjuvant, and first and second line advanced settings. This translational application aims to exploit this achievement. Aims To create a Biliary Tract Cancer Virtual Tissue Bank (BTC VTB) which will make available samples and associated prospectively collected clinical trial data for high quality, peer reviewed and ethically approved research. Methods Tumour blocks from patients across all the UK BTC trials will be sent to UCLH for DNA and RNA extraction, and preparation of tissue microarrays. The locations of all samples collected as part of these trials will be logged in a database. An Access Committee, which will be composed of key stakeholders, will be responsible for approving proposals to use the tissue and data. Applicants will be expected to provide evidence of adequate funding for the proposed research, and will be required to cover the costs of tissue retrieval, including shipping and administration. How the results of this research will be used The research utilising the BTC VTB samples and data should improve our knowledge of the molecular profile of BTCs, identify prognostic markers and predictive markers that will enable selection of treatment most likely to be of benefit.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Young people’s engagement with e-cigarettes and their marketing: a mixed-methods, engaged project to co-produce recommendations for policy
Funder: Cancer Research UK

Abstract: Background: While adults’ use of e-cigarettes appears to be stable, evidence suggests that experimentation among young people has increased. Despite differences in opinion within the public health community regarding the value of e-cigarettes in harm reduction for adults, there is broad consensus on the need to protect young people from this disruptive technology. User-generated and influencer marketing content on social media represents a key influence on young people’s understandings of products. It is essential to monitor the content that young people access related to e-cigarettes, understand how young people relate to that content, and to involve young people in the formulation of policy regarding e-cigarette products and their marketing. Aims: 1) Document the nature of online user-generated and influencer marketing content related to e-cigarettes and explore how young people engage with that content. 2) Explore young people’s responses to, and engagement with, e-cigarettes and the broader e-cigarette marketing environment, including user-generated and influencer content, focusing on different product types and flavours, perceptions of harm and purchasing behaviours. 3) Co-produce with young people evidence-informed recommendations for e-cigarette policy and communication. Methods: The research aims are addressed by three phases of research, supplemented by PPI activities, all conducted with young people aged 11-16. The outcomes of each phase will inform the subsequent phases. Phase 1 comprises a scoping review of user-generated and influencer marketing content on social media popular among teenagers, followed by paired interviews with friendship pairs of young people to understand their engagement with that content. Phase 2 comprises a quantitative survey of young people’s engagement with e-cigarette products and their marketing, building on measures used in past surveys to enable robust, long-term cross-sectional analysis. Phase 3 comprises deliberative workshops to co-produce young people’s recommendations for policy related to e-cigarette products and their marketing. How the results of this research will be used: A series of reports, journal articles and academic presentations will be produced based on the findings of the various parts of this programme of research, and key implications for policy and practice will be disseminated in blog posts and two stakeholder workshops with key parliamentary, third-sector and policy actors. All data generated will be shared with vetted, legitimate research users to enable further examination. Policy recommendations co-produced by informed, engaged young people will help to inform future policy actions and set research agendas.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: EPIC DIVE - Early PancreatIc Cancer Diagnosis In Vivo Evaluation
Funder: Cancer Research UK

Abstract: Background Pancreatic cancer is a lethal disease mainly due to over half of cases being diagnosed at late stages. In the minority of cases diagnosed before cancer spreads, survival reaches 39%. Consequently, there is a clear need for earlier diagnosis using non-invasive strategies that can be applied to high-risk but otherwise asymptomatic populations. Existing approaches for the diagnosis of cancer tend to perform poorly in early stages of disease. This includes approaches based on the detection of circulating tumour DNA (ctDNA) which may be exceedingly rare during early tumour development. Aims The EPIC DIVE project aims to show that it is possible to capture and amplify ctDNA in circulating blood, thus increasing the chances of detecting ctDNA in a blood sample. Towards this aim, our immediate objective is to show that isothermal ctDNA amplification can be performed on nanoclusters in a fluidic system that mimics systemic blood circulation, first using saline solution and then using human blood. Methods The amplification system will use recombinase polymerase amplification (RPA). ctDNA sequences specific to pancreatic cancer will be identified from the published literature. Multiple primer sets targeting the ctDNA target will be designed using RPA primers and tested in optimal conditions for RPA. Amplification will be developed in a stepwise manner, initially on nanocrystalline ZnO in saline solution spiked with target ctDNA. Amplification will next be attempted on prepared nanoclusters and then in a fluidic system to imitate the systemic blood circulation first with saline and then with human blood. Solutions will be spiked with varying concentrations of ctDNA to determine the limits of detection. In parallel, studies will use focus groups to explore general practitioner and patient attitudes towards the use of ex-vivo fluid devices to facilitate early detection of pancreatic cancer. Focus group interactions will be recorded and undergo thematic analysis. How the results of this research will be used If successful, our study will provide evidence that ctDNA can be amplified in an environment that approximates the human circulatory system. Subsequent studies would then verify whether the amplification system can be performed in model systems that more closely resemble the human circulatory system, including animal models. It is hoped that eventually a version of our approach will be trialled in humans and shown to be a safe and non-invasive way to amplify ctDNA in vivo, thus improving the sensitivity of existing ctDNA detection assays to diagnose cancer at early stages.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS