Nottingham

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are investigating how different exercise programs affect pain and daily function in adults with chronic low back pain. This study includes generally healthy adults aged 18 to 45 years who have experienced low back pain lasting more than three months. The study compares usual exercise routines to specific running-based or swimming/cycling-based exercise interventions to see which method might better manage pain and improve function. Participants will be randomly assigned to one of three groups: a control group continuing their usual exercise, a running group, or a swimming/cycling group. Those in the running and swimming/cycling groups will follow an 8-week combined exercise program that includes aerobic activity, strengthening exercises that gradually increase in intensity, and flexibility exercises. The program is designed to promote adherence and reduce injury risk. Throughout the study, participants will complete assessments of their pain and functional ability at the start, after 8 weeks, and at 12 months. These assessments use validated patient-reported outcome measures to track changes over time. Researchers will monitor participants' progress and safety during the intervention and long-term follow-up to understand the short- and long-term effects of these exercise programs on chronic low back pain.

Researchers are investigating BGB-16673, a targeted protein degrader aimed at treating various B-cell cancers including marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, and diffuse large B-cell lymphoma. The study includes both Phase 1 and Phase 2 parts to determine safe and effective dosing and to evaluate the drug's response in patients. The trial is conducted under the new company name BeOne Medicines, previously known as BeiGene. The treatment involves oral administration of BGB-16673. Phase 1 focuses on dose escalation and safety expansion to identify the maximum tolerated dose and recommended dose for expansion over approximately 28 days to 3 years. Phase 2 includes expansion cohorts to assess overall response rates over about 3 years. Participants may have prior treatments including Bruton tyrosine kinase inhibitors and other anticancer therapies depending on their cancer type and study phase. Participants will be monitored closely with assessments of adverse events from the first dose until 30 days after the last dose or before starting new therapy, whichever comes first, for up to 47 weeks. The study measures tolerability, dosing recommendations, and treatment response. Eligibility assessments include performance status and measurable disease, with safety and response evaluations continuing through both phases for up to three years.

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.

This research aims to collect long-term safety and effectiveness data for participants treated with ibrutinib, a medicine used for various blood cancers and conditions including Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Diffuse Large B-cell Lymphoma, Waldenstrom Macroglobulinemia, and Chronic Graft Versus Host Disease. It also provides ongoing access to ibrutinib for participants who have completed previous ibrutinib studies, continue treatment, and benefit from it. This is an open-label Phase 3b study without formal hypothesis testing. Participants will continue their current ibrutinib dosing regimen from the prior study, taken orally once daily as capsules in doses of 560 mg, 420 mg, 280 mg, or 140 mg, around the same time each day. Treatment continues until the investigator decides the participant no longer benefits due to disease progression or side effects, the participant withdraws, alternative ibrutinib access becomes available, or the study ends. Participants not able to access ibrutinib elsewhere can keep receiving the single-agent ibrutinib until all transition or stop treatment, or until the study is stopped. During the study, safety is monitored throughout and summarized, and effectiveness may be analyzed together with previous study data. The main outcome measured is the number of participants experiencing any adverse events within 30 days after the last dose or until starting another cancer treatment. Participants will undergo assessments including pregnancy testing and investigator evaluations to ensure ongoing benefit and safety. The study duration depends on when participants stop treatment or transition to other access.

Neuroblastoma is a common and serious childhood cancer that often leads to death, especially in high-risk cases where the cancer is harder to treat. This trial focuses on children aged one year and older with relapsed neuroblastoma, which means the cancer has come back or is resistant after initial treatment. The study aims to find better treatment combinations to improve survival, evaluate their safety and effectiveness, and learn more about the biology of relapsed neuroblastoma through biomarker research. This is a phase I/II international trial designed to potentially impact clinical practice and advance targeted therapies. Participants will be randomly assigned to one of two main treatment groups receiving combinations of drugs including dinutuximab beta, irinotecan, temozolomide, and bevacizumab, administered every three weeks for up to 12 cycles. A third treatment group with a more experimental combination is also available for a smaller number of patients to confirm dosing and safety before possibly expanding. The trial includes detailed drug regimens and allows for adjustments based on safety and effectiveness findings. During the study, participants will undergo various assessments such as imaging scans, blood tests, and bone marrow evaluations to monitor disease status and treatment effects. Researchers will track progression-free survival and observe any dose-limiting toxicities over up to five years after randomization. Biological samples will be collected to support research on neuroblastoma. Patient quality of life and safety will be closely monitored throughout the treatment and follow-up periods, which together may last up to eight years from enrollment.

Researchers are evaluating the drug STP938, which targets an enzyme involved in DNA and RNA production, as a potential treatment for adults with relapsed or refractory B-cell and T-cell lymphomas. This Phase 1/2 study aims to assess the safety, tolerability, and effectiveness of STP938 in these lymphoma types. The study is divided into two parts: the first focuses on finding the best dose and safety of STP938, while the second examines its effectiveness in treating different lymphoma subtypes. STP938 is given orally as a tablet. The Phase 1 portion involves dose escalation to determine the optimal dose, and the Phase 2 part involves expanding patient groups to study the drug's effects across five different types of B and T cell lymphomas. Throughout the study, blood samples will be collected to understand how STP938 affects lymphoma and the body. Participants will be monitored over an average of 9 months, with researchers evaluating safety, tolerability, and response to treatment. The study will include regular assessments, including clinical evaluations and laboratory tests, to track the drug's impact and patient health. The main outcomes measured are the safety and tolerability in Phase 1 and the objective response rate in Phase 2, reflecting how well the lymphoma responds to the treatment.

Researchers are evaluating the safety, tolerability, and biodistribution of RCT2100, a CFTR mRNA therapy, in a multi-part Phase 2 study involving healthy adults and participants with cystic fibrosis (CF). This first-in-human study aims to provide safety and tolerability data to support future clinical trials. The study includes three parts: a single ascending dose in healthy volunteers, multiple ascending doses in CF patients, and co-administration with ivacaftor in CF patients.