Romford

Researchers are evaluating new treatments for men with prostate cancer that has spread to other parts of the body and still responds to hormone therapy. This Phase 3 trial compares two additional therapies with the best standard care to see if they slow cancer spread and improve survival. Participants from diverse backgrounds across multiple UK hospitals are involved, and the study is managed by University College London. The trial has two main comparisons. In Comparison S, participants receive either standard care alone or with added targeted high-dose radiotherapy (Stereotactic Ablative Body Radiotherapy or SABR) aimed at metastatic lesions. In Comparison P, participants receive standard care alone or with a radioactive drug (177Lu-PSMA-617) that targets prostate cancer cells. Standard care includes long-term hormone-reducing therapy and may include other approved medications or treatments. Treatments are given according to specific schedules: SABR is delivered in 3-5 sessions over 1-2 weeks, while 177Lu-PSMA-617 is given in up to three 6-week cycles. Participants are randomly assigned to either standard care or the new treatment with equal chance. During the study, participants undergo regular scans and tests to monitor cancer and side effects. Doctors track treatment safety and may stop treatment if side effects become serious or participants choose to stop. The main outcome measured is overall survival, with final results expected around 5 to 7 years after the first patient starts treatment. Participants' health status and response to treatment are closely observed throughout the study period.

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 Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are studying the immune response and safety of mRNA-1018-H5, a pandemic influenza vaccine, in adults aged 18 years and older. The trial aims to assess how well two doses of this vaccine trigger antibody production and to monitor any side effects or reactions. This is a Phase 3, randomized, observer-blind, placebo-controlled study focused on the influenza virus. Participants will receive either the mRNA-1018-H5 vaccine or a placebo, both provided as sterile liquid injections. The study involves two doses and includes detailed monitoring for immune response and side effects after vaccination. The trial compares the vaccine to a placebo to evaluate its immunogenicity and safety. During the study, individuals will undergo medical evaluations including physical exams and pregnancy testing if applicable. Researchers will measure antibody levels at Day 43 and record any local or systemic reactions up to Day 29 after injections, as well as any adverse events up to Day 205. The study tracks serious and medically-attended adverse events to ensure careful safety monitoring throughout the participation period.

Researchers are evaluating the efficacy and safety of verekitug (UPB-101) in adults with moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD), a long-term inflammatory lung condition. This global, multicenter Phase 2b study aims to understand how well verekitug works compared to a placebo, alongside participants' usual COPD medications. Participants must have a confirmed COPD diagnosis and meet specific lung function and symptom criteria to join the study. Participants will be randomly assigned to receive one of two doses of verekitug or a matching placebo, in addition to their regular COPD background treatments. The study includes a screening period of about 4 weeks, followed by treatment lasting between 60 and 108 weeks. After treatment, there is a 16-week follow-up period to monitor participants after their last dose. Throughout the study, participants will undergo various assessments including lung function tests and symptom evaluations. Researchers will track the annual rate of moderate or severe COPD flare-ups from the start of treatment through week 108. Safety and tolerability will be closely monitored during the treatment and follow-up periods to ensure participants' well-being over the course of the trial.

Researchers are studying an experimental drug called odronextamab in combination with lenalidomide for adults with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL), which are subtypes of Non-Hodgkin's lymphoma. This Phase 3 study has two parts: Part 1 focuses on the safety and tolerability of this drug combination and determining the appropriate odronextamab dose, while Part 2 compares the effectiveness of this combination to the current standard treatment of rituximab plus lenalidomide. The study also explores side effects, drug levels in the blood, antibody development against the study drug, and impacts on quality of life and daily activities. Participants receive either odronextamab plus lenalidomide or rituximab plus lenalidomide according to the study protocol. Part 1 is not randomized, focusing on safety and dose finding, while Part 2 is randomized and controlled to assess efficacy and safety. Treatments are administered per protocol guidelines during these study phases. During the study, participants undergo regular evaluations including imaging scans to measure disease, blood tests, and monitoring for side effects up to two years. The main outcomes measured include dose-limiting toxicities within 35 days, treatment-emergent adverse events over two years, and progression-free survival over five years. Participants are also monitored for quality of life and ability to perform daily activities throughout the trial duration.

Researchers are evaluating an experimental drug called odronextamab for adults with previously untreated follicular lymphoma, a type of non-Hodgkin lymphoma. This Phase 3 study aims to assess the safety, tolerability, and effectiveness of odronextamab alone and compared to the current standard treatments, including rituximab combined with different types of chemotherapy. The study also examines side effects, drug levels in the blood, antibody responses against odronextamab, and the impact on quality of life and daily activities. The study consists of two parts: Part 1 is non-randomized and focuses on the safety and tolerability of odronextamab given alone. Part 2 is randomized and controlled, comparing odronextamab to rituximab combined with chemotherapy regimens such as CHOP, CVP, or Bendamustine-containing therapies. All treatments are administered according to the study protocol. Participants receive these treatments to evaluate how well odronextamab works versus standard care. Participants will undergo various assessments including imaging scans like CT or MRI to measure disease, blood tests to monitor bone marrow and liver function, and evaluations of side effects up to two years. Researchers will track dose-limiting toxicities within 35 days and assess complete response rates over 30 months. Safety and side effects will be monitored continuously, and quality of life will also be evaluated. The total length of participation depends on treatment and follow-up schedules defined in the protocol.

Researchers are evaluating the safety and tolerability of acalabrutinib, taken as a monotherapy 100 mg twice daily by mouth, compared to the investigator's choice of treatment in adults with chronic lymphocytic leukemia (CLL) who also have moderate to severe heart failure. This Phase IV, open-label, randomized study focuses on patients with cardiac impairment defined by a left ventricular ejection fraction (LVEF) below 50%. The study aims to assess cardiovascular and other adverse events related to these treatments over an extended period. Participants will be randomly assigned to receive either acalabrutinib or a treatment chosen by their investigator, which may include drugs like chlorambucil, venetoclax, ibrutinib, zanabrutinib, rituximab, or obinutuzumab. Treatment cycles last 28 days, with hematology visits at the start of each cycle for the first eight cycles and every four cycles afterward. Cardiology assessments including echocardiogram, ECG, Holter monitoring, cardiac biomarkers, and possibly cardiac MRI will be done regularly during treatment and follow-up. Decisions about treatment changes due to cardiac side effects involve collaboration between the principal investigator and a cardiologist. Patients will be closely monitored through scheduled visits during treatment and after discontinuation, up to four years from the last patient randomized. Assessments include safety checks, cardiac evaluations, disease response per established criteria, and survival status updates every 16 weeks once disease progresses. The study's primary focus is on cardiovascular safety endpoints, including serious and fatal cardiac events, adverse event frequency, and treatment discontinuation rates related to side effects.

Researchers are evaluating two different early treatment methods for adults hospitalized with sepsis, a serious condition caused by the body's extreme response to infection. This study focuses on comparing starting a vasopressor medication called norepinephrine immediately versus the standard approach of first giving fluid through a drip and then adding vasopressors if needed. The goal is to see which method better improves recovery, reduces complications, shortens hospital stay, and enhances long-term health. This is a Phase 3 clinical trial addressing a critical and complex condition with significant risks to patients' organs and survival. The study compares early peripheral vasopressor infusion (PVI) started within 12 hours of hospital admission targeting a mean arterial pressure (MAP) of 65 mmHg or higher, against the usual care involving intravenous fluids followed by vasopressors as needed. Norepinephrine is prepared at a concentration of 16 micrograms/ml and administered either as an early continuous infusion or after fluid resuscitation. Balanced crystalloid fluids are given according to standard care practices. Current guidelines and clinical practices inform the treatment approach, but this study aims to clarify the benefits of early vasopressor use in septic shock. Participants will be monitored for clinical effectiveness during the first 48 hours, with follow-up extending to 90 days after randomization. The study includes assessments such as blood pressure, serum lactate levels, and clinical status evaluations. Researchers will track recovery times, complications, hospital length of stay, and long-term health outcomes. Safety monitoring and evaluation of adverse effects will be ongoing throughout the study period to ensure participant well-being.

Researchers are evaluating the optimal duration of antibiotic treatment for adults with complicated intra-abdominal infections (cIAI). This Phase 3 trial aims to compare a fixed extended duration of 28 days of antibiotics to the current standard care durations, which typically range from 7 to 18 days. The study will assess clinical outcomes, quality of life, and cost effectiveness over a 180-day follow-up period to determine which approach may better reduce treatment failure and improve patient care while considering antimicrobial resistance concerns. Participants will be randomly assigned to one of two groups: the standard care group, where antibiotic type and duration are determined by their clinician, or the fixed extended-duration group, which receives antibiotics for a set 28-day period. The study includes a total of 1166 adult patients recruited from intensive care units and hospital wards across approximately 30 NHS trust hospitals. The treatment period is followed by monitoring up to 180 days after randomization. During the study, patients or their personal consultees will complete quality of life questionnaires at baseline and at 30, 60, and 180 days post-randomization. They will also provide information about antibiotic use and healthcare resource utilization. Researchers will collect hospital records on admissions, relapses, and further infections. The main outcome measured is treatment failure within 180 days of randomization, with safety and effectiveness assessed throughout the follow-up period.