Colchester

This is an open-label (identity of assigned study drug will be known) study designed to collect long-term safety and efficacy data and provide ibrutinib access to participants in completed ibrutinib studies. PCI-32765 (Ibrutinib) is a first-in-class, potent, orally-administered, covalently-binding small molecule inhibitor of bruton's tyrosine kinase. "PCI-32765" and "ibrutinib" refer to the same molecule; hereafter, "ibrutinib" will be used. Participants will continue with the current ibrutinib dosing regimen established in the parent ibrutinib study until the investigator determines that the participant is no longer benefitting from treatment (ie, disease progression or unacceptable toxicity has occurred), the participant withdraws consent, alternative access to ibrutinib is available and feasible (example, participant assistance program or commercial source of ibrutinib), or for other reasons as defined in the protocol, or until the end of the study, whichever occurs earlier. Safety will be monitored throughout the study and summarized. Efficacy may be analyzed in combination with the data collected in the parent protocol. There is no formal hypothesis testing planned for this long-term extension study. Participants for whom alternative access to ibrutinib is not available and feasible can receive treatment with single-agent ibrutinib until end of study, which is defined as the time when all participants still receiving study treatment have transitioned to commercial or alternative access to ibrutinib, have stopped receiving ibrutinib treatment, or upon a decision by the sponsor to terminate the study, whichever occurs earlier.

Immunotherapy with pembrolizumab targeting the T cell inhibitory PD-1 receptor has significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). Approximately 3600 new patients are treated in the 1st line setting per year in England alone and up to 25% remain on 6 weekly pembrolizumab for 2 years. However, pharmacological and clinical trial data suggest current frequent dosing for 2 years result in overtreatment. Indeed, pembrolizumab remains bound to its target receptor for up to 100 days following a single dose and studies in multiple tumour types have found no relationship between dose and patient outcome. Moreover, anti-PD1 treated patients who respond but discontinue therapy either as planned after 2 years, or earlier because of toxicity, can either remain in remission and/or be sensitive to re-challenge with pembrolizumab. REFINE-lung will test whether reduced pembrolizumab dose frequency (9, 12, 15, 18 weeks) after 6 months of standard treatment is safe and effective. This UK study represents a unique opportunity to determine whether pembrolizumab dose frequency can be safely reduced in NSCLC, resulting in significant cost benefits to the NHS and globally, in addition to enhanced patient QoL associated with fewer hospital attendances and reduced toxicity.

The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine (AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A gene.

The purpose of this study is to identify preventive treatments that can minimize the occurrence, severity, and duration of talquetamab-related taste changes (dysgeusia), during the prophylaxis (preventive) treatment phase, and to better characterize the signs or symptoms of talquetamab-related taste changes.

This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).

This study is open to adults with diabetic retinopathy. People who have non-proliferative diabetic retinopathy of moderate or high severity can join the study. The purpose of this study is to find out whether a medicine called BI 764524 helps people with diabetic retinopathy. The study also aims to find a suitable treatment plan for BI 764524. Participants are put into 5 groups by chance. Participants in groups 1, 2, and 3 get BI 764524. Over 1 year, they get a different number of injections of the same dose of BI 764524 injected into 1 eye. During some visits, participants may get a sham control, which is done like an eye injection but without a needle, so that participants will not know how many injections of BI 764524 they received. Participants in group 4 only get a sham control. Participants in group 5 (only in the USA) get aflibercept or sham injections during some visits. Aflibercept is a medicine already used to treat diabetic retinopathy. Participants are in the study for one and a half years. During this time, they visit the study site at least 16 times. During this time, doctors regularly do eye exams and visual tests to assess the severity of participants' eye condition. After 1 year of treatment, researchers look at the number of participants with eye improvements. To do so, they compare eye damage and certain severe eye problems between the groups of participants. The doctors also regularly check participants' health and take note of any unwanted effects.

Eligible patients will be randomised to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine and dacarbazine, with growth factor support). If patients agree, they will have a PET-CT scan after 1 cycle (PET1). The result of this scan will be blinded and used for exploratory endpoints only. Treatment will not be influenced by the result of this scan. All patients will have a PET-CT scan after 2 cycles of treatment (PET2) which will be centrally reviewed. The Deauville score from central review will be used to risk adapt subsequent therapy as follows: * Patients with Deauville score 1-3 will have one further cycle of their randomised chemotherapy and then enter follow up. * Patients with Deauville score 4 will have two further cycles of their randomised chemotherapy followed by involved site radiotherapy * Patients with Deauville score 5 will be withdrawn from trial treatment. They will have further treatment at their treating clinician's discretion and will enter follow up for the trial. Patients with Deauville score 4 on PET2 will have a final PET-CT scan to confirm adequate treatment response. Patients will be followed up for a minimum of 5 years after completing treatment.

This is a multi-centre, randomised, non-inferiority, phase III study in patients with low risk differentiated thyroid cancer. Patients will be identified via oncology multidisciplinary team meetings. There will be two sources of patients in the trial, with the same histological diagnoses and prognosis (i.e. recurrence risk): * Group 1: Patients who have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC will be randomised 1:1 to undergo surveillance only OR a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy). * Group 2: Patients diagnosed with low risk DTC using cytology (Thy5) but no surgery performed will be randomised 1:1 to have either a hemi-thyroidectomy OR a single-stage total thyroidectomy. The overall aim of the trial is to determine whether hemithyroidectomy is an acceptable and cost-effective surgical procedure compared to total thyroidectomy in low risk thyroid cancer. Overall, 456 patients will be recruited to the trial. Patients will be initially be followed up post-surgery then 12 monthly for 6 years.

Participants will take part in a feasibility trial whilst they are on the ESNEFT physiotherapy waiting list to avoid disrupting their routine care. Participants will first attend a face-to-face eligibility assessment to validate their diagnosis of PFP, before being randomised to one of two arms: 1. The online education arm will be provided with password access to our online patient education platform (https://www.teampfp.com/my-knee-cap-pain) that contains four modules; \[a\] Understand your pain; \[b\] How do I start to exercise; \[c\] Treatment options; \[d\] Case studies. The aim of each module is to provide people with knowledge they can put into practice (experiential learning) and facilitating their self-management. A short quiz at the end of each module assesses user engagement and knowledge retention. Investigators developed these modules alongside members of the International Patellofemoral Research Network, and people with PFP that attended a PPI event at Queen Mary University London (QMUL) that aimed to understand what information people with PFP wanted to help them self-manage their condition. Participants randomised to the online education group will be instructed to consume the content at their own pace (with one module/week advised) and that their adherence will be determined by monitoring their completion of each end of module quiz. Participants with no access to a device or the internet, will be given a paper version. 2. The control arm will receive no additional care whilst on the ESNEFT physiotherapy waiting list. Their involvement in the trial will end at six-weeks follow up and they will then be provided with access to the online education platform if they request it. The feasibility outcomes, adapted from those used in recent trials and mapped to trial quality appraisal scales, are designed to inform us on the willingness of clinicians to recruit participants, the willingness of participants to be randomised, if participants will accept and adhere to patient education intervention, if sufficient data can be collected, and potential effects of online education. Outcomes informing intervention effects have been optimised after discussion with participants from two pre-trial PPI focus groups. Outcome measures will be collected using the good data protection regulations (GDPR) compliant REDCap system (https://www.project-redcap.org/). Participants will receive regular prompts and paper versions with stamped/addressed envelopes will be available to those who are digitally illiterate, supported by a research assistant. 1. Recruitment and eligibility; a recruitment rate of four eligible participants per month is targeted, with consent rate (eligible/consenting participants) calculated 2. Randomisation and blinding; broad equality of baseline characteristics between groups and acceptable outcome assessor blinding will be targeted 3. Adherence and acceptability; \>75% of participants in the online education arm attempting the end of education module quizzes and acceptability meaningfully greater than remaining on a waiting list 4. A maximum 20% attrition rate in either arm 5. Data collection; with \>85% of participants completing all outcome measures at six-week follow up targeted. 6. The 7-point Likert global rating of change (GROC) scale will be used to allow comparison to recent RCTs involving people with PFP. Categories will be: \[1\] much better, \[2\] better, \[3\] a little better, \[4\] no change, \[5\] a little worse \[6\] much worse, and \[7\] markedly worse. Successful outcome will be dichotomised and defined a priori as \[1\] much better or \[2\] better at six-weeks follow up. 7. An eleven-point numerical pain rating scale (NPRS) will assess worst pain in the past week, which is valid and responsive in people with PFP 9. 8. The reliable and responsive EQ-5D-5L will assess health-related quality of life; important for future cost-effectiveness analyses 16. The final question of EQ-5D-5L relates to anxiety/depression. If participants select severely or extremely anxious or depressed, the investigators will inform the participant's GP. Investigators will invite a subset of participants randomised to the online education arm to participate in a maximum of two semi-structured focus groups (n=6 per group) or 1:1 interviews post-trial. The aim of these focus groups will be to explore their perspectives on participating in our feasibility trial and receiving our online patient education intervention. Investigators will specifically explore the factors that affected if participants felt they had benefitted from receiving online patient education, and whether further physiotherapy input was still required. These semi-structured focus groups will be conducted by co-applicant Dr Katharine Fowler.

The only phase III clinical trial in the UK offering watch and wait, the TRIGGER trial aims to validate mrTRG as an imaging biomarker for the stratified management of patients with locally advanced rectal cancer. The 'good responders' (mrTRG1\&2) often have no evidence of tumour and it may be possible to avoid surgery in this group and so maintaining QoL while not impacting survival rates. The 'poor responders' (mrTRG3-5) are at high risk of poor oncological outcomes and this knowledge is useful in planning ongoing treatment and surveillance. TRIGGER is now a non-cTIMP trial as the protocol does not specify chemotherapy or IMP treatments. Decisions about the use of chemotherapy will be based upon local MDT discussions as is normal practice and national policy and the trial CRFs will capture these decisions and whether more treatment is given to patients or not. TRIGGER does not mandate or recommend the use of any treatments: specifically it does not suggest the use of investigational medicinal products. If any centre wishes to use IMPs this would be in the context of separate trial protocols and would not preclude entry into TRIGGER.