Groningen

Researchers are evaluating the Breathlessness diagnostics in a Box (BiaB) tool to see if it can shorten the time to diagnose the cause of breathlessness in patients. This study uses a prospective stepped-wedge cluster design in general practice settings across the Netherlands, Spain, and Portugal. The goal is to compare usual care with the BiaB intervention, also assessing if BiaB increases diagnoses of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), as well as its usability and efficiency. The study involves 45 general practice sites, each participating for 40 weeks. All sites begin with a usual care period and then sequentially switch to the BiaB intervention period following a predetermined schedule. The BiaB tool supports healthcare professionals during routine clinical care by aiding in the assessment of patients presenting with breathlessness. Participants have a single study visit and may complete up to four quarterly questionnaires over a maximum follow-up of one year. Data are collected during routine visits, from electronic medical records, and through questionnaires completed by patients and healthcare professionals. The main outcome measured is the time from first consultation with breathlessness to diagnosis, tracked for up to 40 weeks per site.

Researchers are evaluating whether the introduction of dedicated hospital-based HIV teams can improve HIV testing rates among patients with HIV indicator conditions across ten European countries. This real-world, multicenter, stepped-wedge cluster randomized effectiveness-implementation trial spans four years and involves hospitals in the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. The study aims to address the current gap in HIV testing and improve early diagnosis by comparing testing rates before and after the implementation of HIV teams. The intervention involves creating local HIV teams led by HIV specialists, supported by nurses and data collectors. These teams focus on auditing and providing feedback to healthcare professionals to encourage HIV testing when indicated, reducing stigma, educating staff on HIV prevention and care, and improving linkage to local prevention services. The HIV teams use electronic health records to identify patients with HIV indicator conditions and integrate their activities into routine hospital care. Participants' data are collected retrospectively from routine care and prospectively at the healthcare professional level. Researchers measure changes in HIV testing rates, new HIV diagnoses, and variations across countries and specialties. They also assess the HIV diagnosis and care cascade, healthcare professionals' knowledge and stigma levels, and implementation outcomes such as resource use and cost-effectiveness. Monitoring includes feedback loops and evaluation of barriers and facilitators to implementation, aiming to improve HIV testing and care sustainability in hospitals.

Researchers are investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the safety, effectiveness, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

Carcinoma of unknown primary origin (CUP) refers to a group of cancers where metastatic disease is present, but the original tumor is not found despite thorough diagnostic tests. This condition limits treatment options since the primary tumor, which guides therapy decisions, remains unidentified. The study aims to use a new PET-CT scan with a radiotracer called [18F]F-fluoro fibroblast activation protein inhibitor (F-FAPI) to detect the primary tumor in CUP patients. This is a prospective clinical study involving 50 patients aged 18 years and older who have already undergone standard diagnostic work-up including FDG PET-CT without identifying the primary tumor. Participants will undergo a one-time [18F]F-FAPI PET-CT scan at one of six study centers. The images will be centrally reviewed, and results along with recommendations for further tests or treatment will be shared with the treating physician. After six months, the PET-CT findings will be compared with patient follow-up data including clinical, radiological, and pathological outcomes. These results will be discussed in a multidisciplinary meeting to evaluate the clinical usefulness of the [18F]F-FAPI PET-CT scan for CUP patients. During the study, patients will have only this single PET-CT examination with [18F]F-FAPI. Researchers will monitor the detection rate of the primary tumor over two years. The main outcome measured is whether the primary tumor is identified by the scan. Safety and any impact on patient care will also be assessed through follow-up and clinical evaluations. The total duration of patient involvement includes the initial scan and a six-month follow-up for outcome comparison.

Researchers are evaluating a new scan called FAPI-PET/CT to detect metastases in patients with advanced gastric cancer. The study aims to find out how well this scan identifies metastases and whether it reduces the burden on patients compared to current methods. Key questions include how often the scan changes treatment plans, such as avoiding unnecessary surgeries or switching to palliative care, and how it affects the diagnostic process with additional biopsies or surgery adjustments. Participants will receive the intravenous drug [18F]-FAPI-74 one hour before undergoing the FAPI-PET/CT scan. This scan is done after initial staging with gastroscopy and a contrast-enhanced CT but before a staging laparoscopy. Based on the scan results, the medical team will decide the next steps, which may include biopsy confirmation of suspect lesions or performing diagnostic laparoscopy if the scan is negative. During the study, participants will have one additional scan lasting about two hours (excluding travel) and complete several questionnaires totaling around four hours. Researchers will track changes in treatment intent for about one year and monitor changes in diagnostic work-up immediately after clinical staging involving FAPI-PET/CT and other diagnostic procedures. Safety and treatment decisions will be closely followed throughout the study period.

Researchers are evaluating the safety and effectiveness of rilzabrutinib compared to placebo in adults with active Immunoglobulin G4 Related Disease (IgG4-RD). This Phase 3, randomized, double-blind study aims to measure the time until the first IgG4-RD clinical disease flare during a 52-week treatment period. Additional goals include assessing disease control, flare-free rates, use of glucocorticoid rescue, and monitoring safety through adverse events, laboratory tests, and electrocardiograms. Participants will be randomly assigned to receive either oral rilzabrutinib tablets or placebo for 52 weeks. Glucocorticoids may be used as rescue medication if needed. The study includes a screening period lasting 4 to 6 weeks before treatment begins, followed by the 52-week double-blind treatment phase, and a 2-week follow-up after treatment. An optional open-label extension lasting up to 108 weeks is also available for participants. During the study, participants will attend 16 visits for assessments, which may include clinical evaluations, imaging tests such as CT, MRI, PET, or ultrasound to monitor disease activity, and laboratory tests. Researchers will track time to disease flare and collect data on flare-free rates, safety parameters, and medication use. Participants' vaccination status and contraceptive use will be monitored according to local guidelines, and overall study participation could last up to 60 weeks or longer if joining the extension phase.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are studying BAY 3713372, a new drug being developed to treat solid tumors with a specific genetic change called MTAP deletion. The drug works by blocking a protein called PRMT5, which may kill cancer cells with this deletion while sparing normal cells. This first-in-human study aims to understand the safety, how the body processes the drug, and its effectiveness in people with these MTAP-deleted solid tumors. Participants will receive BAY 3713372 orally every day. The study starts with a dose escalation phase, where different groups get increasing doses to find a safe and effective dose. After this, a dose expansion phase will include more participants receiving the drug alone or with other treatments. Participants can continue treatment as long as they benefit and do not experience severe problems. During the study, participants will visit the study site multiple times before and during treatment, and follow-up visits after treatment ends. Doctors will monitor health through blood and urine tests, heart checks with electrocardiograms, and imaging scans like CT or MRI to track cancer changes. Tumor samples may also be taken. Safety and treatment response will be closely assessed, including adverse events and how the drug behaves in the body. Participants will be contacted every three months for up to two years after treatment to check their health.

Researchers are evaluating the safety and effectiveness of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as initial treatments for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC) whose tumors express PD-L1. This Phase III, randomized, double-blind, global study focuses on patients whose tumors meet the PD-L1 expression threshold of 1% or higher and do not have certain genetic mutations or rearrangements that would require other targeted therapies. Participants receive either rilvegostomig or pembrolizumab intravenously on the first day of each 21-day treatment cycle. Both groups also receive platinum-based chemotherapy drugs such as carboplatin or cisplatin, administered intravenously up to four cycles, along with pemetrexed given intravenously on Day 1 of each cycle. The study monitors these treatments as first-line therapy for metastatic non-squamous NSCLC. During the study, participants undergo regular assessments including imaging scans to measure tumor size and response, as well as evaluations of organ and bone marrow function. Researchers track overall survival and progression-free survival for up to approximately five years. Safety is closely monitored throughout, and patients are followed long-term to assess outcomes related to treatment effectiveness and tolerability.