Maastricht

Researchers are evaluating a "wait-and-see" approach for patients with rectal cancer who respond completely to neoadjuvant chemoradiotherapy. This study aims to provide both short-term and long-term data on cancer control and patient function when surgery is avoided in good responders. The research also seeks to establish a national network of expert centers to improve organ-preserving care and create a registry to gather more evidence about this treatment strategy. The standard treatment for locally advanced rectal cancer typically involves chemoradiotherapy followed by surgery. In this study, patients who show a complete clinical response after treatment will be observed without immediate surgery under a "wait-and-see" policy. The study is a multicenter prospective observational cohort and implementation study, focusing on patients aged 18 or older who have had a long course of chemoradiotherapy or a short course with a long waiting interval. The main goal is to track disease-free survival without tumor regrowth over two years. Participants will be closely monitored using clinical exams, endoscopy, and advanced MRI scans to confirm their response and detect any regrowth early. Researchers will measure outcomes such as two-year disease-free survival, regrowth rate, local control, overall survival, quality of life, and the ability of centers to provide high-quality organ preservation care. Patients will undergo intensive follow-up to ensure safety and gather comprehensive data on the effects of this less invasive approach over time.

Researchers are investigating the accuracy of two PET scan tracers, 18F-FDG and 68Ga-FAPI-46, in detecting the extent of estrogen receptor-positive (ER+) breast cancer. This is important because the standard 18F-FDG tracer may not detect distant metastases well in ER+ breast cancer due to its lower metabolic uptake compared to other breast cancer subtypes. The study aims to find out if the newer tracer, 68Ga-FAPI-46, which targets a protein common in many tumors, can better identify cancer spread and improve treatment decisions for these patients. This is a phase 2 pilot study focused on patients with locally advanced, recurrent, or metastatic ER+ breast cancer. Participants will undergo the usual 18F-FDG PET/CT or PET/MRI scan for staging their breast cancer, followed by additional imaging using 68Ga-FAPI-46 PET/CT and PET/MRI before starting treatment. Both PET scans will be performed within 20 working days to compare their diagnostic accuracy directly. The study evaluates the detection rate of cancer lesions by each tracer to see if 68Ga-FAPI-46 offers better imaging for this breast cancer subtype. During the study, patients will be monitored from diagnosis until all imaging exams are completed. Researchers will collect data from the scans to determine which tracer identifies cancer spread more effectively. The primary outcome is to establish key parameters needed for calculating the sample size for a larger diagnostic accuracy study. Patients must consent to all procedures, and their safety and ability to complete the imaging tests will be closely observed throughout the study period.

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 whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

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 low-grade and high-grade gliomas to better understand why current treatments are not curative and to explore the causes of tumor diversity, dedifferentiation, invasion, and treatment failure. This study aims to create patient-derived organoids (PDOs) from glioma tumors to identify mechanisms behind malignancy and resistance to therapies, potentially leading to more effective personalized treatment options. The study involves establishing three-dimensional PDO cultures from both newly diagnosed and recurrent low-grade and high-grade gliomas. These organoids will be genetically, phenotypically, epigenetically, and transcriptomically characterized to compare them with the original tumors. Researchers will also investigate the effects of various treatments, including immunotherapy, chemotherapy, and radiation, alone or in combination, on these organoids. Additional goals include developing co-cultures with immune cells and studying radiation-induced cell death and tumor dedifferentiation. Participants will undergo tumor resection for organoid development and blood sampling at baseline. Researchers will analyze the organoids and parental tumors for genetic and molecular profiles. The study focuses on detailed profiling and treatment testing to predict survival and quality of life outcomes for glioma patients. Participation involves clinical and laboratory evaluations centered around the tumor tissue and blood samples.

This research aims to study the safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug VX-670 in adults who have Myotonic Dystrophy Type 1 (DM1). The trial involves participants aged 18 to 64 years with a confirmed diagnosis of DM1, including a genetic test showing a specific CTG repeat count. The study is a Phase 1/2 trial designed to assess how the drug behaves and how well it is tolerated in this population. Participants will receive VX-670 or a placebo, both administered intravenously, in single and multiple dose escalations. The study is randomized, double-blind, and placebo-controlled to compare the effects of the drug against a non-active treatment. The treatment periods include initial dosing and extended follow-up to evaluate responses over time. During the study, researchers will monitor participants closely for any adverse events from the start up to 42 days in the initial phase and up to 168 days in the extended phase. Safety and tolerability will be the main focus, alongside collecting data on how the drug is processed by the body and its biological effects. Participants will undergo assessments to track these outcomes throughout their involvement in the trial.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

Researchers are evaluating the safety and effectiveness of the Adaptive Tip Catheter (ATC) as a first-line direct aspiration thrombectomy method for patients experiencing an acute ischemic stroke. This study focuses on patients with stroke symptoms in the anterior circulation who can receive endovascular treatment within 24 hours of their last known well time. Eligible participants are adults aged 18 to 90 years with specific stroke severity and imaging scores. Participants will undergo mechanical thrombectomy using the Adaptive Tip Catheter. The procedure is performed as the first treatment approach to remove blood clots causing the stroke. Treatment must begin within 24 hours of symptom onset, defined by the time of access puncture. The study includes only one intervention group using this device. During the study, researchers will assess reperfusion success during the procedure through independent imaging review. Participants will be monitored for safety and treatment outcomes, including stroke severity scores and imaging assessments. Informed consent is required before enrollment, and the total study involvement includes evaluations before, during, and after the thrombectomy procedure to ensure safety and effectiveness.

Researchers are evaluating the use of epigenome-guided treatment selection compared to the usual standard-of-care (SOC) treatment in adults with active Crohn's Disease (CD) who are starting biologic therapy. This multicenter, prospective, randomized, controlled, open-label study aims to assess the efficacy, safety, and cost-effectiveness of this approach by comparing clinical remission and endoscopic response at Week 26. About 378 participants with active CD, defined by specific clinical and endoscopic criteria, will be included, with roughly half being biologic-naive and the other half exposed to no more than one prior biologic treatment. Participants will be randomly assigned to either receive biologic therapy guided by an epigenetic biomarker assay and the EpiPredict software, which predicts response to two biologics (Vedolizumab or Ustekinumab) or to receive treatment selected according to usual SOC without epigenome guidance. Biologic therapies will be administered following product labels and local SOC recommendations, with dose adjustments allowed as needed. Study assessments will follow the SOC schedule for each biologic during the 26-week treatment period, with different visit weeks depending on the biologic used. Participants will undergo blood sample collection for epigenetic testing during screening. Study visits will include clinical and endoscopic assessments at specified weeks, with long-term follow-up every six months up to 24 months after Week 26 using medical records and questionnaires. Researchers will measure outcomes related to clinical remission and endoscopic response, safety, and cost-effectiveness. Participants' adherence and ability to comply with protocol requirements will be monitored throughout the study.