NIHRDataInsights/HRCSData huggingface dataset:
Title: Routine assessment of symptoms, functioning, social difficulties and quality of life of cancer patients to improve the process and outcomes of care.
Funder: Cancer Research UK

Abstract: We, and others have shown in randomised trial, that routine use of computer-based technologies to evaluate patient-centred aspects of cancer care is possible. The data can be readily provided to physicians, resulting in improvements in patient well-being. The value of this approach to patient care has been proved in principle. In the next 5 years, we will develop and refine the approaches and seek to enhance their impact by: - Improving the content of the evaluations; - Developing them in ways that engage professionals to ensure that they are widely and effectively used; - Demonstrate the enhanced value of these approaches in rigorous clinical research. The specific aims are: 1. To implement regular patient-reported assessment of symptoms, social difficulties, psychological distress and quality of life in oncology practice. To evaluate the impact on process of care and patient outcomes using randomised clinical trials. 2. To continue the development (or adaptation) of measurement tools for use in daily practice, using qualitative (focus groups, interviews) and statistical approaches (Rasch analysis). Outline plan of research: 2 related projects are proposed. 1. Automated assessments of patient-reported outcomes and their implementation in oncology practice. - Exploratory studies of patient acceptability of improved questionnaire package and investigation how oncologists use the information, to inform physician training; - Randomised trial to test the improved intervention (questionnaire package and physician training). 2. Automated assessment and social difficulty detection - Exploratory studies of implementation of Social Difficulties Inventory (SDI) in clinical practice


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS
Title: Cambridge Institute: Functional follow up of GWAS studies
Funder: Cancer Research UK

Abstract: Functional follow up of GWAS studies Our research focuses on how polygenic variation contributes to susceptibility to breast and lung cancer. We analyse mechanisms both at single loci, and at the level of gene regulatory networks. Our aims are 1) to improve recognition of high risk groups within the population and 2) ultimately, to devise strategies for prevention based on mechanisms of risk. The class of uncommon, strongly predisposing, mutations in cancer susceptibility genes, such as BRCA1 and 2 in breast and ovarian cancer, are important because of their significant risks to individuals. But BRCA mutations account for fewer than 5% of breast cancers, and for only about 20% of the estimated total inherited susceptibility. The remaining 80% of susceptibility is thought to be ‘polygenic’: that is, the result of the combined effects of many hundreds or thousands of common and rare genetic variants, each making a small contribution. Our group published the first cancer GWAS in 2007, identifying five loci for predisposition to breast cancer. Since then world-wide efforts have identified another 80 breast cancer loci, which collectively account for about 14% of the estimated susceptibility. In lung cancer, only a small number of loci, accounting for less than 5% of susceptibility, have been identified. We face two related problems: 1) identification of the loci which account for the as yet unexplained ‘missing heritability’ and 2) elucidation of the mechanism by which the genetic variants have their effect. To date, these problems have been tackled one locus at a time. As outlined below, we and our colleagues have continued this approach. However, given that there are probably hundreds of loci of diminishing effect, it seems that this analysis can never be anywhere near complete. The effects of the weaker loci will be too small to detect in even the largest imaginable GWAS, and the labour of functional dissection of each individual locus will be too great. Moreover, in reality the genetic variants are having their effects, not one by one but in combination; in interaction with each other and with the environment. This suggests that some measurement of the combined effect might provide an integrated readout of the risk of all the variants and their interaction with the environmental exposures in that individual, and perhaps an indication of the mechanisms involved.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/06/024: RT3 VIN: A randomised phase II multi-centre trial of topical treatment in women with vulval intraepithelial neoplasia
Funder: Cancer Research UK

Abstract: Background: Vulval intraepithelial neoplasia (VIN) has a significant invasive potential, predominantly affects premenopausal women, is often highly symptomatic and difficult to manage clinically. Surgery is often chosen as the treatment for this condition but is associated with high rates of recurrence and may be mutilating. By comparison, recent small studies of new topical treatments have shown promising results that warrant further investigation as an alternative to surgery. Relevance to cancer: The exact incidence of VIN in the UK is unknown but is increasing, especially in younger women. Also unknown are the exact progression rates, but the incidence of unexpected invasion found during histological analysis of surgical excision specimens is approximately 15%. Aims of the research: Primary: To determine whether either of the topical treatments, Cidofovir or Imiquimod, show sufficient activity to warrant further investigation in a phase III setting. Secondary: To determine whether these treatments are safe and feasible to use. Outline Plan: Patients with biopsy proven VIN3 who are suitable to receive a topical treatment by a specialist clinical team will be allocated to receive either Cidofovir or Imiquimod. Patients who have previously failed on Imiquimod following a treatment regimen of thrice weekly applications for a minimum of 12 weeks will receive only Cidofovir. Complete responders will be followed up for at least 2 years after completion of treatment.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/026: ADAM: A randomised stratified phase II multicentre clinical trial of single-agent ADI-PEG 20 (pegylated arginine deiminase) in patients with malignant pleural mesothelioma
Funder: Cancer Research UK

Abstract: Background to the proposal Malignant pleural mesothelioma (MPM) is an increasing health burden on many societies worldwide, and being generally resistant to conventional treatment, has a poor prognosis with a median survival of less than 1 year. Relevance to cancer We have identified an 'Achilles heel' in this tumour, relating to arginine synthesis, first characterised in patients with liver cancer and melanoma. We showed that arginine depletion induced selective apoptosis of mesothelioma cell lines lacking the enzyme argininosuccinate synthetase. Since arginine is an essential amino acid for up to 70% of MPM tumours on account of AS deficiency, arginine depletion as a therapeutic modality warrants clinical investigation (Proc AACR 2006; abs 2206). Specific aims of research We seek to test the efficacy of arginine depletion in patients with AS negative malignant mesothelioma. Patients will be given treatment for 6 months. We will assess progression rate 6 months from enrollment (primary endpoint), response rate and overall survival. Outline plan of research The trial design is a randomised phase II study. Eighty-four chemonaive patients with stable MPM (performance status 0 or 1) will be recruited from four centres (Barts, Belfast, Hull, and Manchester). Patients will be randomised to receive either best supportive care (BSC) or BSC and a weekly intramuscular injection of the arginine lowering drug, ADI-PEG 20 (Phoenix Pharmacologics, Inc). Patients will be assessed clinically every 4 weeks and radiologically every 8 weeks. Blood and tumour samples will be collected for detailed laboratory analysis. Patients will be offered chemotherapy on progression.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/012: TNT: triple negative breast cancer trial: A randomised phase III trial of carboplatin compared to docetaxel for patients with metastatic ER- PR- HER2- breast cancer
Funder: Cancer Research UK

Abstract: The TNT trial will identify if a platinum drug is more effective than a taxane drug (the standard of care) in ER-ve PR-ve HER2-ve breast cancer. This proof of principle trial will test evidence suggesting that a gene called BRCA1 may not function normally in some breast cancers of this type, and therefore that patients may require a different approach to chemotherapy treatment.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/08/006: CUP-ONE: A multi-centre phase II trial to assess the efficacy of epirubicin, cisplatin and capecitabine in carcinomas of unknown primary (CUP): incorporating the prospective validation of molecular classifiers
Funder: Cancer Research UK

Abstract: Background and relevance to cancer: Although Cancers of Unknown Primary (CUP) are among the top ten commonest cancer diagnoses, they are under-researched. Their prognosis remains poor, with no consensus on optimal treatment. Conventional clinical methods to identify and classify the origin of CUP have been unhelpful. Specific Aims: The main aims of this pilot study are to determine the feasibility of combining the established chemotherapy regimen epirubicin, cisplatin and capecitabine (ECF) with Erlotinib (ECX-Er), in CUP. This incorporates and compares novel molecular classification techniques for classifying tumours for prediction of primary site of origin, as well as exploratory assessments for correlation with response and prognosis Plan of research: This is a randomized pilot phase II study of ECX +/- Er, in CUP. The study has two parts with separate consents: - Part One is a prospective double-blinded validation of three diagnostic classifiers on metastatic biopsies, a proportion of which will remain classified as CUP after clinical work-up. - Part Two is the therapeutic study: an open-label pick-the-winner two-arm randomised phase II trial in CUP. The primary end-point is progression-free survival. A total of 114 patients gives a 90% probability that the true winner is picked if the hazard ratio is 1.3. The study also incorporates a Simon's two-stage phase II minimax procedure to establish whether an acceptable response rate is achieved. < Last updated 21/07/2010


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Molecular classification of carcinomas of unknown primary (CUP): Diagnostic validation and correlation with clinical outcomes with epirubicin, cisplatin, capecitabine with and without Erlotinib (ECX-Er)
Funder: Cancer Research UK

Abstract: Background and relevance to cancer: 10-15% of cancers present with metastatic disease. In up to one-third of these patients, no tumour site of origin is found. This cancer of unknown primary (CUP) is common, yet is under-researched. The prognosis is poor and there is no consensus on optimal management, partly because current therapies for adenocarcinomas, which form most CUPs, are tailored to their site of origin. Specific aims: We aim: to validate and compare three molecular classifiers for the prediction of primary site in patients with metastatic disease, including true CUP; and to correlate the molecular and clinical CUP-ONE data. Plan of research: The study has two parts with separate consents. The CUP-ONE trial will recruit around 360 patients with metastatic disease which is of unknown origin at presentation. Such patients invariably undergo biopsy of the metastasis. Paraffin-embedded (and where possible fresh-frozen) tissue will be collected and submitted for classification using immunohistochemistry, RT-PCR and microarray analyses (in Glasgow, Melbourne and Amsterdam) (Part One of study). In the majority of patients, subsequent clinical investigation should reveal a definite primary site which can be compared to the primary site(s) independently predicted by the three molecular classifiers. Where no site of origin is found (true CUP), patients may enter Part Two, the therapeutic study: an open-label phase II trial of epirubicin, cisplatin and capecitabine (ECX) with the primary end-point of progression-free survival. The molecular predictions (and underlying expression profiles) will be correlated with the clinical data including therapeutic response and outcome.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/005: CONVERT: A 2-arm randomised controlled trial of concurrent chemo-radiotherapy comparing twice-daily and high dose once-daily radiotherapy in patients with limited disease small cell lung cancer
Funder: Cancer Research UK

Abstract: (1) Background to the proposal There is increasing evidence in favour of early concurrent chemoradiation for the treatment of limited stage small cell lung cancer. The Turrisi trial has established early concurrent twice-daily (BD) chemo-radiotherapy as standard treatment for this group of patients. However there has been concern that the toxicity of BD thoracic irradiation concomitant with chemotherapy is too high and that the treatment is logistically difficult to deliver. The Turrisi trial has not been repeated and it is important to establish whether this BD concept is effective and whether these results could be improved. (2) Relevance to cancer To establish a standard chemo-radiotherapy regimen in patients with LD SCLC and good performance status (3) Specific aims of the research The trial aim is to potentially improve on the results of the Turrisi regimen by increasing the total radiotherapy dose given once daily, using conventional fractionation. The trial will also provide us with toxicity and outcome data for the Turrisi regimen using modern radiotherapy techniques (conformal radiotherapy without elective nodal irradiation). (4) Outline plan of research A 2-arm multi-centre randomised trial comparing once daily (66Gy/33 fractions) and twice daily (45Gy/30 fractions) radiotherapy schedules (given concurrently with cisplatin/etoposide) in the treatment of patients with limited-stage SCLC and good performance status.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/009: CHORUS: A randomised trial to determine the impact of timing of surgery and chemotherapy in newly diagnosed patients with advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma
Funder: Cancer Research UK

Abstract: Surgery followed by chemotherapy is standard treatment for ovarian cancer. There are potential advantages of chemotherapy given both before and after surgery. Women are being treated this way without evidence that it is as effective as standard treatment. CHORUS will help determine whether this new approach can be adopted without compromising effectiveness.


Research activity codes: 6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/07/023: SIOPEL 6: A randomised phase III trial of the efficacy of sodium thiosulphate in reducing ototoxicity in patients receiving cisplatin chemotherapy for hepatoblastoma
Funder: Cancer Research UK

Abstract: Most children with standard risk hepatoblastoma, treated with cisplatin chemotherapy and surgery, are cured. Three year overall survival is 91%. However 60% of these children will have acquired permanent cisplatin induced hearing loss. This randomised trial will introduce a chemoprotectant, sodium thiosulphate, with the goal of reducing this side effect.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development of highly precise dose-escalated, intensified radiotherapy techniques for treating lung and head-and-neck tumours
Funder: Cancer Research UK

Abstract: Background and relevance to cancer Radiotherapy is one of the most common non-surgical treatments of cancer. Over the last twenty years substantial advances have been made in radiotherapy physics, leading to the widespread implementation of high-precision photon beam techniques. Notable improvements in prostate and head-and-neck outcomes have been achieved. The goal of this proposal is to further improve radiotherapy of squamous cell head-and-neck (HNSCC) and non-small cell lung (NSCLC) cancers. Results are currently good but improvable for HNSCC, but poor for NSCLC. However several factors impact similarly on NSCLC and HNSCC treatment design - dose acceleration circumvents tumor repopulation but is limited by early reactions; dose escalation is limited by late complications; and normal structure doses can be minimised using very modern techniques (tomotherapy and intensity modulated arc therapy - IMAT) which deliver many intensity-modulated fields. Specific aims and research plan In four linked pieces of work, biophysical methods will be developed and used to optimise dose-distributions and fractionation schedules, aiming to further improve radiotherapy outcomes. 1. Modelling of early reaction dose-time dependence will be improved, and model datafits used to investigate likely effects of nonstandard (chemo-) irradiation schedules. (Year 1) 2. Pneumonitis and oesophagitis dose-time-volume data obtained from clinical trials of 3 different fractionation schedules will be analysed. (Years 3-4). 3. Sequential PET FLT images will be collected for cohorts of 10 NSCLSC and HNSCC patients, and MRI-BOLD hypoxia images will be collected for a further 10 HNSCC patients. Topological and chronological variations in FLT uptake and hypoxia will be analysed, exploring the potential of selective boosting of rapidly proliferating or hypoxic tumor subregions, and of adaptive modification of treatment schedules. (Years 1-6) 4. Novel mathematical optimisation approaches particularly suited to arc-based radiotherapy will be developed, aiming to design an IMAT planning system more interactive than any current intensity-modulated software. (Years 1-6)


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CRUKD/08/044 A CR-UK Phase I/II trial of abiraterone acetate in patients with ER+, PR+ or AR+ refractory metastatic breast cancer
Funder: Cancer Research UK

Abstract: Despite improvement in the outcome of patients with metastatic breast cancer with the introduction of endocrine therapy, acquisition of resistance to endocrine therapy remains problematic. There is now irrefutable pre-clinical and epidemiological data supporting the role of adrenal steroids (e.g. DHEA, DHEA-S) in breast carcinogenesis. Not only are these steroids positively associated with breast cancer and cell proliferation, they have also been shown to directly activate ER±. Inhibition of the production of these adrenal hormones could potentially yield therapeutic benefits. In addition, in vitro studies have shown that breast cancer cell lines become hypersensitive to very low level of oestradiol following long-term oestrogen deprivation. Since adrenal steroids can function as weak agonists of ER±, these steroids could activate a hypersensitive AR. Finally, an irrefutable body of data indicates that the androgen receptor is expressed in a significant proportion of breast cancers (both ER+ and ER-) and that AR is functional in these tumours. We therefore hypothesize that the inhibition of CYP17 by abiraterone, will safely inhibition the generation of DHEA, DHEA-S, androstenedione as well as testosterone, dihdrotestosterone and oestrogens and have important antitumour activity in women with ER+, PR+ or AR+ metastatic breast cancer. We propose a Phase I study to examine the safety and tolerability of this agent, and Phase II study to assess its efficacy. Characterisation of patients' endocrine profiles (pituitary-adrenal-gonadal axis), tumour ER, PR and AR status, and circulating tumour cells will be undertaken.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: PROM: Predicting Relapse of Melanoma at High Risk of Recurrence
Funder: Cancer Research UK

Abstract: Background and Relevance to Cancer Although the majority of melanoma patients are cured by surgery, those with thick, ulcerated primary tumours and/or nodal involvement have a high risk of relapse and death. AVAST-M is a randomised trial to evaluate the potential for bevacizumab, an anti-VEGF antibody, to prevent relapse in patients with melanoma at high risk of recurrence. Bevacizumab can occasionally be toxic and is expensive, both in terms of drug costs and the staff involved in its administration. Identification of patients suitable for treatment, and/or most likely to benefit, would be very useful. Specific Aims of the Research: We wish to identify markers in patients' blood or tumours that predict (i) whose melanoma will relapse, and (ii) whose risk of relapse is affected by bevacizumab treatment. Outline Plan of Research: Tumour samples, already obtained as part of patients' treatment, will be analysed for expression of markers relevant to bevacizumab's mechanism of action, and these related to clinical outcomes. Other markers thought to affect the probability of melanoma relapsing will also be examined. Blood samples obtained before treatment, where given, and every 3 months for a year will also be tested.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: POETIC: Trial of Perioperative Endocrine Therapy - Individualising Care
Funder: Cancer Research UK

Abstract: To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) followed by standard adjuvant therapy improves outcome compared with standard adjuvant therapy alone in postmenopausal women with hormone receptor positive breast cancer. To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for relapse free survival (RFS) in the individual patient more effectively than the pre-treatment Ki67 value. To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than at diagnosis. TRIAL DESIGN: Phase III, multi-centre, randomised trial. Patients will be allocated in a 2:1 ratio to PERIOPERATIVE THERAPY with an AI for 4 weeks (two weeks before and two weeks after surgery) or NO PERIOPERATIVE THERAPY. PATIENT TYPE/NUMBER: Postmenopausal women with ER/PgR positive primary breast cancer. The trial aims to recruit at total of approximately 4000 patients. TRIAL TREATMENT: Group I: PERIOPERATIVE THERAPY with an AI Choice of AI is according to centre policy and may be either anastrozole (1mg/day) or letrozole (2.5mg/day) Group II: NO PERIOPERATIVE THERAPY TREATMENT DURATION: 4 weeks (two weeks before and two weeks after surgery) ENDPOINTS: Primary endpoints: •Relapse free survival (clinical endpoint) •Proliferation rate (Ki67) at baseline core biopsy and at surgical excision (biological endpoint) Secondary endpoints: •Time to local recurrence •Time to distant recurrence •Overall survival •Breast cancer free survival •Gene expression profile at core biopsy and at surgical excision (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4023)


Research activity codes: 5.1 PHARMACEUTICALS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS