Burton On Trent

Researchers are evaluating whether reducing the frequency of pembrolizumab treatment after six months of standard therapy is safe and effective for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab, an immunotherapy targeting the PD-1 receptor on T cells, has improved outcomes for this condition. Because pembrolizumab remains bound to its target for a long time and dosing frequency may not affect outcomes, this study aims to find out if less frequent dosing can maintain effectiveness while reducing overtreatment and side effects. This phase III study also considers potential benefits like cost savings and improved quality of life due to fewer hospital visits. Participants who have completed six months of pembrolizumab treatment without disease progression and are continuing therapy will be randomly assigned to receive pembrolizumab at the standard six-week interval or at a reduced frequency of 12 weeks. If early results show that the 12-week schedule is not less effective, later participants may be randomized to even longer intervals of 9, 15, or 18 weeks. Pembrolizumab is given intravenously at 400 mg per dose. Patients whose disease progresses on a reduced frequency schedule may return to the standard six-week treatment. During the study, researchers will monitor overall survival at two years after randomization. Participants will undergo regular assessments to track disease status, treatment tolerability, and overall health. The study aims to confirm that less frequent dosing does not reduce survival while potentially improving patient experience. The trial is open to adults aged 18 and older with advanced NSCLC who have already completed six months of pembrolizumab therapy and intend to continue treatment.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

This research aims to understand the genetic factors that contribute to the risk of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). GCA is a serious inflammatory disease affecting blood vessels, mainly in people over 50, which can cause severe complications like vision loss or stroke if untreated. PMR causes pain and stiffness in the limbs with signs of inflammation. The study involves both patients recently suspected of having GCA and those with confirmed diagnoses from the past. It seeks to provide new insights into disease causes and improve diagnosis and treatment approaches. Participants are observed in a multi-center study collecting clinical and genetic data. The study includes both prospective patients with suspected GCA and retrospective patients with confirmed GCA or PMR diagnoses. Some retrospective participants receiving tocilizumab for recurring or difficult-to-treat GCA are also included in a safety monitoring registry. Data collected include clinical features, imaging, tissue and blood samples, and advanced genetic testing. The study also follows patients over time to assess disease impact, quality of life, and long-term outcomes. During the study, participants provide medical information, biological samples, and complete questionnaires about their symptoms and quality of life. Researchers monitor disease activity and treatment effects, especially among those starting certain immune-modifying drugs. The main measurements focus on genetic susceptibility at the study start, with ongoing evaluation of diagnosis, prognosis, and disease progression. The study is designed to improve understanding and management of GCA and PMR over time.

Researchers are investigating the safety and effectiveness of adding olaparib, a PARP enzyme inhibitor, to platinum-based chemotherapy given before surgery in patients with triple-negative breast cancer (TNBC) and/or those with germline BRCA (gBRCA) mutations. This randomized phase II/III trial aims to see if this combined treatment improves the rate of pathological complete response (pCR) at surgery while monitoring safety outcomes. The study plans to enroll at least 780 patients, including a minimum of 220 with gBRCA mutations. Participants will receive a minimum of 21 weeks of chemotherapy followed by surgery. The treatment includes oral olaparib tablets taken twice daily about 12 hours apart, alongside intravenous paclitaxel and carboplatin given in cycles every three weeks. During the trial, standard supportive care like granulocyte-colony stimulating factor and anthracyclines may also be administered. For those with residual disease after initial treatment, there is an option to join a sub-study involving additional chemotherapy drugs. Throughout the study, patients will undergo screenings including BRCA mutation testing and various tumor marker assessments. Safety will be closely monitored by the trial team and an independent committee. The main outcomes measured are treatment-related side effects, pCR rates after surgery, and long-term efficacy assessed over approximately 5.5 years, with follow-up planned for up to 10 years after surgery.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are evaluating if using additional liver diffusion weighted MRI (DW-MRI) scans at diagnosis can find more synchronous liver metastases than CT scans alone in patients with high risk colorectal cancer. This phase II multicenter study focuses on patients with advanced primary colorectal tumors who have no evidence of liver metastases on CT scans. The goal is to improve detection and management of liver metastases by sharing MRI findings with multidisciplinary teams for treatment decisions. Participants will undergo additional breath hold T1, T2, and DW-MRI liver scans without intravenous contrast every six months for three years after surgery. Any liver metastases detected on these scans will be reviewed by the local multidisciplinary team and treated following local protocols. This ongoing monitoring aims to identify metastases early and guide appropriate therapy. During the study, participants will have regular imaging assessments and clinical evaluations as part of their post-surgery surveillance. The researchers will measure the presence of liver metastases through these MRIs and track treatment responses. Findings will be discussed in multidisciplinary team meetings, and participants will be followed for five years after the last recruitment to assess long-term outcomes and management of liver metastases.

Researchers are investigating the Avantect test, a new blood test designed to detect pancreatic cancer early in patients recently diagnosed with type 2 diabetes. Pancreatic cancer is highly lethal, often detected too late for curative treatment. The study focuses on adults aged 50 to 84 years who were diagnosed with type 2 diabetes within the past six months, as this group has a significantly higher risk of undiagnosed pancreatic cancer. The trial aims to evaluate if the Avantect test can identify pancreatic cancer at a treatable stage, potentially improving survival rates. Participants will be randomly assigned to either an intervention group or a control group. Those in the intervention arm will have their blood samples tested with the Avantect device soon after collection. If the test detects biomarkers suggesting pancreatic cancer, participants will be informed and offered imaging scans such as MRI or CT to confirm diagnosis. Control group samples will be stored for future testing or research. The study will enroll up to 15,000 participants over three years. Each participant will attend three study visits over a 12-month period, providing blood samples and completing anxiety questionnaires at every visit. Researchers will follow all participants remotely via cancer and mortality registries for three years after enrollment to track any cancer diagnoses. The main outcomes measured include the sensitivity and specificity of the Avantect test and the rate at which pancreatic cancer can be surgically removed, with analyses planned at six months and at three years.

The trial investigates the role of ixazomib in patients with relapsed multiple myeloma who have previously undergone autologous stem cell transplant (ASCT). This phase III, open-label, randomized, controlled study aims to evaluate whether adding a proteasome inhibitor to the salvage ASCT conditioning improves the depth of response, and to assess the impact of consolidation and maintenance treatments on the durability of response. The study also looks at overall survival, progression time, quality of life, and treatment safety among participants with measurable disease and good performance status. All participants first receive re-induction therapy consisting of 4 to 6 cycles of ixazomib, thalidomide, and dexamethasone (ITD) over 28-day cycles to achieve maximum disease control. Those who reach stable disease or better are randomized to receive either conventional ASCT using melphalan or augmented ASCT combining melphalan with ixazomib. Following this, participants who maintain minimal response or better undergo a second randomization to either receive consolidation therapy with 2 cycles of ITD followed by ixazomib maintenance until disease progression, or no further treatment. During the study, participants will undergo regular assessments including blood tests, disease response evaluations, and monitoring for adverse effects. The primary outcomes measured are overall response rate 100 days after ASCT and progression-free survival up to 10 years. Secondary evaluations include overall survival, time to disease progression, minimal residual disease status at various stages, engraftment kinetics, and quality of life. Follow-up continues with clinic visits every three months until disease progression is observed, enabling long-term monitoring of treatment effects and safety.