NIHRDataInsights/HRCSData huggingface dataset:
Award Title: CRUK/11/010 IoN: Is ablative radioiodine Necessary for low risk differentiated thyroid cancer patients - a randomised trial
Funder: Cancer Research UK

Abstract: Background:
 Radioactive iodine (RAI) ablation is standard practice along with total thyroidectomy and thyroid stimulating hormone suppression (TSHS) therapy for differentiated thyroid cancer, but all the evidence comes only from observational studies. However, there is a subgroup of patients who have a low risk of recurrence, and there is uncertainty over whether routine RAI ablation is beneficial or represents over-treatment. Furthermore, it has potential side effects including increased risk of second cancers and is associated with significant financial costs to the health service.

 Aims:
To evaluate whether the 5-year recurrence(disease)-free survival rate among patients not given RAI ablation is no worse than those who do have RAI ablation (using cytologically or histologically confirmed structural loco-regional recurrent or residual disease and distant recurrence).

Methods:
This is a prospective randomised controlled phase III trial. Patients likely to have low risk of recurrence will be randomised to RAI ablation (1.1 GBq) or No ablation following total thyroidectomy. All patients have TSHS therapy and will undergo surveillance with neck ultrasound, stimulated thyroglobulin and standard thyroid function tests. Fifty percent of patients will in addition receive RAI ablation and a post ablation scan as per standard practice. All patients will be followed up every 6 months (from ablation/stimulated Tg timepoint) for 5 years and then as per site local practice thereafter.

How the results of this research will be used:
The results could have the potential to change clinical practice in the UK and internationally, and mean that these patients could avoid having RAI ablation, which would be of benefit to both patients and a cost saving to sites.


Research Activity Codes: 6.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/11/051: IRCI 001 - A Phase III randomised trial of gemcitabine plus docetaxel followed by doxorubicin versus observation for uterus limited, high grade uterine leiomyosarcoma (International Rare Cancers Initiative study - IRCI 001)
Funder: Cancer Research UK

Abstract: Background: Uterine leiomyosarcoma (ULMS) is rare but even patients with early-stage disease have a 50-70% chance of relapse/recurrence of disease.
Recurrences may be distant or local or both. Adjuvant pelvic radiation can decrease local recurrence rates, but has not been shown to increase overall survival. Previous adjuvant trials have been conducted in a mixed population of sarcomas which may not reflect the potential benefit in ULMS. A recent phase II study of adjuvant gemcitabine plus docetaxel (GT) followed by doxorubicin (D) for women with uterus-limited high grade LMS was conducted by the Sarcoma Alliance for Research through Collaboration (SARC). The result was that 78% of women with uterus-limited LMS treated with adjuvant GT followed by D remain progression-free at 2 years, with median follow-up of 27.3 months which is improved over historical controls. An international rare cancers collaborative has been established to allow a sucessful phase III trial.
 Aim: To assess whether adjuvantchemotherpay (SARC GT-D regimen) improves survival in high grade uterine LMS.
Methods: International 1:1 Randomised phase III clinical trial of GT-D after surgery versus at the point of relapse with primary endpoint of overall survival. Secondary endpoints: whether GT-D imporves recurrence-free survival, evaluate predictors of recurrence and response.
Results will be used to determine the future standard of care for patients with ULMS and factors which will determine chemotherapy use and response.


Research Activity Codes: 6.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/12/037: NCRI CLL10 - Phase III trial to assess ibrutinib+R against FCR in newly diagnosed patients with Chronic Lymphocytic Leukaemia (CLL)
Funder: Cancer Research UK

Abstract: Background: Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in the UK. The most effective therapy for CLL is the combination of fludarabine, cyclophosphamide and rituximab (FCR). FCR is the standard therapy for patients who are fit for relatively intensive therapy. However FCR is associated with significant early and late toxicity mainly with infections, bone marrow suppression, the risk of secondary myelodysplasia and acute myeloid leukaemia. FCR is not curative so all patients will inevitably relapse and most will eventually die from CLL. An understanding of the pathophysiology of CLL is leading to the development of novel therapies and the most promising approach utilizes therapies that target signaling through the B-cell receptor (BCR), which is expressed on CLL cells and leads to CLL cell proliferation. This approach results in impressive responses with minimal toxicity in patients with chemotherapy refractory CLL. Ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase, a critical component of BCR signaling, is one of the leading agents in this new therapeutic class.
Aims: The aim of this research is to test whether the cytotoxic chemotherapy component of CLL therapy (i.e. fludarabine and cyclophosphamide), which leads to many of the complications of therapy, can be replaced by targeted therapy with ibrutinib thereby improving responses, duration of remission and survival with reduced toxicity. We will assess the safety and efficacy of ibrutinib in combination with rituximab (IR) in previously untreated patients with CLL compared to the current standard treatment of FCR.
 Methods: This is a Phase III, multi-centre, randomised, controlled, open, parallel group trial in patients with previously untreated CLL comparing IR with FCR. The principal research question is to assess whether IR is superior to FCR in terms of progression-free survival. Secondary objectives are to assess response rates, overall survival, MRD negativity, CLL growth rates after relapse,safety and toxicity, quality of life and health economics.
How the results of this research will be used: The results of the trial will potentially redefine the standard therapy for CLL removing the need for chemotherapy and thereby reducing short and long-term toxicity, reducing relapses and the subsequent development of refractory disease.


Research Activity Codes: 6.1 PHARMACEUTICALS;6.2 CELLULAR AND GENE THERAPIES
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/12/040: IELSG 37 - A randomised, open-label, multicentre, two-arm phase III comparative study assessing the role of involved mediastinal radiotherapy after rituximab containing chemotherapy regimens to patients with newly diagnosed primary mediastinal B-Cell lymphoma (PMBL)
Funder: Cancer Research UK

Abstract: Primary mediastinal B-cell lymphoma (PMBL) principally affecting young adults. Initial therapy is critical in PMBL as salvage therapy for recurrence or progressive disease is often of limited efficacy; thus, there is an imperative to cure the disease at the first attempt. A tension however exists between achieving the highest possible cure fraction and minimising long-term toxicity in survivors. Uncertainty
exixts as to whether consolidation radiotherapy to the mediastinum is necessary following immunochemotherapy and
whether PET scanning can be used to discriminate patients who require radiation therapy from those who do not.

This is a prospective international randomised non-inferiority phase III trial. Patients with previously untreated PMBL will be enrolled on the basis of the clinical and local pathologic characteristics of and with consent, be preregistered before the start the chemotherapy.

All patients will undergo a pretreatment PET/CT and then go on to receive one of the standard chemotherapy regimens (e.g., CHOP14/21, DA-EPOCH, Mega-CHOP, ACVBP, VACOP-B or MACOP-B) in association with at least 6 courses of Rituximab (R-chemotherapy). The PET/CT scans will be repeated at 5-6 weeks (i.e. day 29-42) after the last R-chemotherapy administration.

 After mandatory central PET/CT, all patients with a negative-PET/CT scan after completion of R-chemotherapy (either with complete or partial radiological regression of the mediastinal mass), will be randomised to receive consolidation mediastinal involved field radiotherapy (IFRT) (control arm) or observation (experimental arm). IFRT (30 Gy) will commence within 6-8 weeks (i.e. day 36-56) after the last administration of immunochemotherapy.

Patients with a partial response and with a positive PET/CT scan will not be randomised and will be treated according the investigator choice (e.g., with IFRT or salvage chemotherapy plus ASCT with or without IFRT). They will be followed for investigator-assessed response to chosen strategy, progression, and survival. All randomised patients will continue participation in the treatment follow-up phase study for 60 months from randomisation. At 10 years from randomisation, long term safety information will be collected.

The primary endpoint is 2-year progression free survival following randomisation, with the secondary endpoint of overall survival and long-term safety analysis. The trial is powered to determine a non-inferior outcome in patients not receiving IFRT based on a sample size of 376 patients. The expected proportion of PET negative cases following R-Chemotherapy is 0.5, so at least 752 patients will need to be enrolled. It is expected that this large staudy will define the standard of care for PMBL.


Research Activity Codes: 7.1 INDIVIDUAL CARE NEEDS
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/13/010: UNIRAD SC - UNIRAD Sample Collection
Funder: Cancer Research UK

Abstract: Background
Although remarkable progress has been made in the treatment of breast cancer, a significant number of patients with ER positive early breast cancer remain at risk of relapse, especially those patients with extensive lymph node involvement (4N+) at diagnosis. The UNIRAD study will investigate whether the addition of everolimus to standard adjuvant endocrine therapy can decrease the rate of disease relapse in patients with ER positive, HER2 negative breast cancer with extensive lymph node involvement.

There is significant interest in non-invasive methods of elucidating the biomarkers predicting which patients are at highest risk of relapse and understanding the tumour evolution steps causing it.

Aims
The translational sub-studies embedded within UNIRAD will investigate the changes to cell free DNA (cfDNA) throughout the trial treatment, as well as the question as to whether cfDNA reflects the primary tumour, or the lymph node metastases,
via comparisons with primary, lymph node and recurrent tissue (if available) with the aim of identifying predictive and prognostic changes (Part 1). Primary tumour samples will also be analysed for markers of mTOR activation that may predict response to everolimus treatment and/or disease relapse (Part 2).

Methods
UNIRAD is a double-blind, multicentre, phase III randomized trial of patients with poor prognosis (4+ involved lymph nodes) ER+ and HER2- primary breast cancer who remain disease-free after 3 years of adjuvant endocrine therapy. The trial is sponsored by a French academic trial group (UNICANCER). Eligible patients will be randomised 1:1 to receive either: everolimus (10mg/day) or placebo (2 tablets/day) added to standard care endocrine therapy for 2 years. The total sample size will be 1984 patients, with approximately 750 patients from the UK. Diagnostic, FFPE tissue samples will be collected from primary, lymph node and future sites of relapse (if applicable) from all UK patients and blood samples at baseline, 4, 12, 18 and 24 months.

How results will be used
The clinical results of the trial will provide a potential evidence base for the use of everolimus in the treatment of patients with ER positive, HER2 negative early breast cancer who are at high risk of relapse. Correlative science results may identify a subgroup of patients most likely to benefit from such treatment and identify patients with the highest risk of disease relapse.


Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/19/016 PEARLS: A phase II/III trial of Primary radiothErapy for Androgen sensitive pRostate cancer patients with Lymph nodeS
Funder: Cancer Research UK

Abstract: Background
Prostate cancer is the most common male cancer in the UK with around 47,000 men diagnosed per year. Around 22% of these men present with disease that has spread outside the prostate. Patients presenting with disease that has spread only to the lymph nodes are likely to represent a favourable subgroup who may be curable with aggressive multi-modality treatment. 

Aims
The PEARLS trial aims to show that, compared to standard field radiotherapy, extended field radiotherapy covering the prostate, pelvis and para-aortic lymph nodes improves metastasis-free survival (MFS) in prostate cancer patients with involved lymph nodes at presentation.

Methods
PEARLS is a multi-stage randomised controlled trial. Men with histologically confirmed prostate cancer with radiographically positive nodal disease on PSMA-PET/CT within the pelvis +/- para-aortic region receiving androgen deprivation therapy +/- androgen receptor targeted therapy or docetaxel chemotherapy are eligible. Patients will be randomised (1:1) to standard field intensity modulated radiotherapy (IMRT) (control arm) or extended field IMRT (experimental arm) with stratification by extent of lymph node disease determined by PSMA-PET/CT (pelvic only vs. para-aortic). All participants will receive IMRT given in 20 fractions over 4 weeks. In the control arm, participants will receive 62 Gray (Gy) to the prostate (and 44Gy to the pelvis with integrated boost of 51Gy to the involved lymph nodes for patients with pelvic-node disease only). In the experimental arm participants will receive 62Gy to the prostate and 44Gy to the pelvis and para-aortic region with a 51Gy boost to involved lymph nodes. In the first stage (phase II, n=150) the primary endpoint is acute lower gastrointestinal RTOG grade 2+ toxicity. If unacceptable toxicity is seen in the first 75 participants receiving extended field radiotherapy then recruitment will stop; otherwise the study will continue. In stage 2 (phase III, n=893; inclusive of the patients within phase II) the trial has 85% power (5% 2-sided significance) to detect a hazard ratio of 0.62 for MFS (an increase from 80% to 87% in 5-year MFS) in 714 participants with pelvic lymph node only disease. In selected centres, participants will be asked to donate blood, tissue and stool samples and undergo PSMA-PET/CT imaging for translational research.

How the results of this research will be used?
Results will contribute to international guidelines for the use of para-aortic radiotherapy in this population and, if positive, will lead to a change in clinical practice.


Research Activity Codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health Categories: CANCER AND NEOPLASMS
Award Title: CRUK/21/010: LOGGIC- Phase III, randomised, international multicentre trial for children and adolescents with low-grade glioma
Funder: Cancer Research UK

Abstract: Background
LOGGIC Core and LOGGIC Europe are two studies in the UK, which are part of larger European studies addressing questions in children and young adults (up to 21) with paediatric low grade glioma (pLGG).

pLGG is the single most common form of brain/spinal cord tumour. They can occur anywhere in the brain and spinal cord, however the tumours can behave very differently. Some tumours require surgery alone, and others may require many lines of treatment including chemotherapy and radiotherapy. Traditionally pLGG have been treated with chemotherapy as a first line. As of yet we cannot predict which pLGG will grow, nor can we predict how patients will respond to treatment in both the short and long term. Most patients (90%) will survive their tumour, however they may do so at a cost to their neurological function and quality of life. All pLGG are thought to be activated by the MAPK pathway, which is normally used to promote growth and development. MEK inhibitors (MEKi) block this pathway, and have shown effectiveness in control of pLGG in small studies. These small studies in children, in addition to larger studies in adults have shown MEKi to be safe and associated with mild side effects.

Aims
LOGGIC Core will undertake detailed testing of approximately 500 pLGG in the UK. It will aim to improve diagnostic accuracy and describe groups of pLGG that behave in a similar way. It will also aim to identify markers in the tumour or child that predict response to treatment.

LOGGIC Europe will aim to identify the best treatment regimen for pLGG with respect to disease control, improvement of neurological behaviour and/or visual function.

Methods
All consented pLGG patients will have the first level of molecular testing in the UK. This will inform which treatments or clinical trials are appropriate for the patient. Further detailed testing of the tumour and patient’s blood will be undertaken in Heidelberg (Germany)

LOGGIC Europe: All consented patients will be randomised to either vincristine/carboplatin (chemotherapy) or vinblastine (chemotherapy) or trametinib (MEKi). The best treatment will be picked based on disease control, neurological behaviour and vision.

Results:
The results of LOGGIC Core will allow us to have a comprehensive understanding of the biology of pLGG, and ways to predict the behaviour of patients and these tumours to treatment. LOGGIC Europe will inform us of the best type of treatment for children with pLGG.


Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS
Award Title: CaRi- Heart for predicting cardiac risk in suspected  coronary heart disease (CAD) (DAP67)
Funder: Department of Health and Social Care

Abstract: Coronary artery disease affects around 2.3 million people in the UK. It is caused by a build-up of fatty plaques on the walls of the blood vessels that supply the heart muscle. This can reduce the flow of blood to the heart and result in people experiencing chest pain (angina) especially when they exercise. Over time, the fatty plaques can grow and block more or all of the artery and blood clots can also form, causing blockage. A heart attack happens when the supply of blood to the heart muscle is blocked._x000D_
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People who have episodes of chest pain, who’s doctors think that they may have coronary artery disease, can have a type of imaging (CT coronary angiography) which shows whether there is any narrowing of their coronary arteries. When offering treatment, specialist heart doctors are likely to consider a person’s symptoms and other risk factors (such as family history of heart disease, diabetes, and smoking history), as well as how much narrowing of the arteries has occurred, how long is the affected area, the location of the affected area. Medicines, such as statins or aspirin, can be used to reduce the risk of fatty plaques growing or blood clots forming. For more serious disease, procedures may be used to unblock the arteries (angioplasty) or to allow blood to flow round the blockage (bypass)._x000D_
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Some people, whose CT coronary angiography imaging results show that they have no or only a small amount of narrowing of their coronary arteries, go on to have heart attacks over the next ten years. For some people this will be because new coronary artery disease has developed during this time. However, it is thought that inflammation of the coronary arteries, which is not detected by CT coronary angiography, can also increase the risk of heart attack._x000D_
CaRi-Heart® is a computer programme that can be used, with CT coronary angiography imaging, to detect inflammation of the coronary arteries. The programme uses information about inflammation of the coronary arteries and other information (such as age, sex, smoking status, diabetes status, cholesterol) to estimate an individual’s risk of dying from a heart attack in the next eight years._x000D_
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This assessment will consider whether the information provided by the CaRi-Heart® software has the potential to change how patients are treated so that the numbers of deaths from coronary artery disease are reduced.

Lay Abstract: The overall aim of this project is to provide a comprehensive summary of all available evidence that may be relevant to the evaluation of CaRi-Heart®, as an adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected CAD, who are undergoing CTCA.

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: CARDIOVASCULAR
Award Title: Can early specialist orthotic assessment lead to improved rehabilitation outcomes and reduced complications for patients following a stroke? (OTIS)
Funder: Stroke Association

Abstract: Background: Delayed orthotic intervention for the lower limb following stroke can negatively impact on stroke survivor’s recovery and contribute to secondary conditions such as contracture. Research is needed to determine the therapeutic value of early orthotic management. 
Aims:
1. To identify the current evidence base for early orthotic intervention.
2. To reach expert consensus on the content of the early orthotic intervention.
3. To investigate the feasibility of conducting a randomised controlled trial to evaluate early orthotic intervention for stroke survivors.
4. To explore stroke survivor and clinician’s experiences of early orthotic intervention.
Methods:
A systematic review to determine the evidence base for lower limb orthotic interventions after stroke will be conducted. The results will be reviewed alongside recent national survey findings using a nominal group technique to reach expert consensus on the content of the early orthotic intervention. A feasibility RCT will be conducted with 30 stroke survivors with lower limb weakness or spasticity, randomised to receive usual care or early orthotic intervention. Follow-ups conducted at 2 and 6 months. Qualitative interviews with up-to 15 participants and stroke clinicians to explore their experiences.
Expected Outcomes: The study will provide key feasibility outcomes to inform a future definitive study.

Lay Abstract: Background: Delayed orthotic intervention for the lower limb following stroke can negatively impact on stroke survivor’s recovery and contribute to secondary conditions such as contracture. Research is needed to determine the therapeutic value of early orthotic management. 
Aims:
1. To identify the current evidence base for early orthotic intervention.
2. To reach expert consensus on the content of the early orthotic intervention.
3. To investigate the feasibility of conducting a randomised controlled trial to evaluate early orthotic intervention for stroke survivors.
4. To explore stroke survivor and clinician’s experiences of early orthotic intervention.
Methods:
A systematic review to determine the evidence base for lower limb orthotic interventions after stroke will be conducted. The results will be reviewed alongside recent national survey findings using a nominal group technique to reach expert consensus on the content of the early orthotic intervention. A feasibility RCT will be conducted with 30 stroke survivors with lower limb weakness or spasticity, randomised to receive usual care or early orthotic intervention. Follow-ups conducted at 2 and 6 months. Qualitative interviews with up-to 15 participants and stroke clinicians to explore their experiences.
Expected Outcomes: The study will provide key feasibility outcomes to inform a future definitive study.

Research Activity Codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health Categories: STROKE;MUSCULOSKELETAL