Maastricht

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the diagnostic performance of two PET tracers, 18F-FDG and 68Ga-FAPI-46, in female patients with estrogen receptor-positive ER breast cancer. This pilot study focuses on patients with locally advanced, recurrent, or metastatic breast cancer and aims to determine if 68Ga-FAPI-46 detects more lesions than 18F-FDG, potentially leading to more accurate staging and treatment decisions. The study is sponsored by Maastricht University Medical Center and is conducted as a Phase 2 interventional trial. All participants will undergo an additional 68Ga-FAPI-46 PETCT and PETMRI scan before starting breast cancer treatment. These imaging exams will be performed within 20 working days from diagnosis and alongside the standard 18F-FDG PETCT or PETMRI scans. The study focuses on comparing these two diagnostic tracers accuracy in detecting cancer lesions in ER breast cancer patients. Participants will be followed from diagnosis until both PET exams are completed. The researchers will collect data to help calculate sample size for future studies and explore the feasibility of taking biopsies from lesions identified by the new tracer. Safety and ability to complete imaging procedures will be monitored. The total participation duration covers the time needed to conduct both imaging exams and any related assessments.

Carcinoma of unknown primary origin CUP is a group of cancers where metastatic disease is present but the original tumor cannot be found despite extensive tests. This condition limits treatment options since therapies often target known primary tumors. Researchers are evaluating whether a new imaging test called 18FF-fluoro fibroblast activation protein inhibitor F-FAPI PET-CT can detect the primary tumor in patients diagnosed with CUP after standard diagnostic scans including FDG PET-CT. This multi-center, prospective clinical study involves 50 adult patients with CUP to better understand the usefulness of this new scan method. Each participant will undergo a single 18FF-FAPI PET-CT scan at one of the six study centers. Images from this scan will be centrally reviewed and shared with the treating doctor, who may recommend further tests or treatments based on the findings. After six months, results from the F-FAPI PET-CT will be compared with clinical, radiological, and pathological follow-up data. A multidisciplinary panel will then review all information to decide how valuable the 18FF-FAPI PET-CT is for identifying the primary tumor in CUP patients. Participants will be involved in one main scanning visit and followed for six months through routine clinical assessments. The study team will monitor detection of the primary tumor using the new scan as the main outcome, and also assess the tests accuracy measures like sensitivity and specificity. Participation requires being able to undergo the scan and complete follow-up, with the entire process lasting about two years for outcome measurement. This study is sponsored by Erasmus Medical Center.

Researchers are evaluating new treatments for advanced renal cell carcinoma RCC, a type of kidney cancer. This study compares the effects of combining two targeted therapies, belzutifan and zanzalintinib, against belzutifan with a placebo. The goal is to see if the combination can help people live longer and prevent the cancer from getting worse after other treatments have failed. Participants will take 120 mg of belzutifan orally and either 60 mg of zanzalintinib or a matching placebo once daily for about 24 months. The study is randomized and double-blind, meaning neither participants nor researchers know who receives the active combination or placebo. Two groups are compared belzutifan plus zanzalintinib and belzutifan plus placebo. During the study, participants will be monitored for progression-free survival and overall survival, with assessments up to around 30 to 50 months. Researchers will also evaluate tumor response, duration of response, quality of life, and side effects. Safety and tolerability will be tracked throughout treatment and follow-up periods. The study is sponsored by Merck Sharp & Dohme LLC and aims to provide important information on treating advanced RCC.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

Researchers are investigating new treatments for locally advanced or metastatic urothelial cancer UC, a type of bladder cancer that has spread or cannot be removed by surgery or radiation. This trial evaluates whether sacituzumab tirumotecan sac-TMT, an experimental medicine, can help people with UC who have already been treated with specific therapies live longer compared to those who receive certain non-platinum chemotherapy options. The study is a Phase 3 randomized trial comparing sac-TMT with chemotherapy drugs selected by the investigator. Participants are assigned to one of two groups one receives sacituzumab tirumotecan at a dose of 4 mgkg every two weeks by intravenous infusion until the disease worsens or side effects become unacceptable. The other group receives one of three chemotherapy drugspaclitaxel, docetaxel, or vinflunineby intravenous infusion every three weeks, also until disease progression or unacceptable toxicity. Rescue medications may be given as needed to manage side effects according to approved guidelines. During the study, participants undergo assessments of overall survival up to about 40 months, along with other measures such as progression-free survival, response rates, duration of response, and quality of life evaluations using questionnaires. Safety is monitored by recording adverse events and treatment discontinuations. The total study participation may last several years, with regular evaluations to understand the effects and tolerability of the treatments.

Researchers are studying high-grade and low-grade gliomas to better understand why these brain tumors behave differently within and between patients and why current treatments often fail. This research aims to uncover how gliomas become more aggressive, spread, and resist therapies by using patient-derived organoids PDOs, which are three-dimensional tumor cultures grown from patients tumor tissue. The ultimate goal is to develop personalized tumor models to test new treatments that could improve survival and quality of life for glioma patients. The study involves collecting tumor tissue from patients diagnosed with either low-grade or high-grade glioma who are scheduled for tumor removal surgery. The tissue will be used to grow PDOs that closely resemble the original tumors. Researchers will analyze these organoids for their genetic, epigenetic, and cellular characteristics and test how they respond to standard and new treatments, including chemotherapy, immunotherapy, and radiation with photons or protons. Additionally, the study will explore interactions between tumor organoids and immune cells, as well as mechanisms of tumor cell death and progression. Participants will undergo tumor resection and blood sampling at baseline to provide tissue for organoid creation and analysis. The research team will monitor the phenotypic and molecular profiles of the organoids to understand tumor behavior and treatment response. This observational study does not involve experimental treatments for participants. Participation involves providing tumor tissue during planned surgery, with no additional treatment changes. The study will continue until December 2028, focusing on advancing knowledge to guide future glioma therapies.

Researchers are evaluating the safety, tolerability, and how the body processes and responds to VX-670 in adults with Myotonic Dystrophy Type 1 DM1. This study is a Phase 12 trial that compares different doses of VX-670 to placebo in people diagnosed with DM1 who have a confirmed genetic test showing a specific repeat in their DNA. Participants will be randomly assigned to receive either single or multiple doses of VX-670 or matching placebo. The study has two parts Part A focuses on single ascending doses, while Part B includes both single and multiple ascending doses. The dosing levels in Part B will be based on results from Part A. Both VX-670 and placebo are given as intravenous solutions. During the study, participants will be monitored for adverse events up to 42 days in Part A and 168 days in Part B to assess safety and tolerability. Researchers will measure drug concentrations in blood plasma and muscle at various time points, including baseline, days 15, and 120. Muscle biopsies will be used to analyze changes in gene splicing. The total participation duration varies by study part, with detailed monitoring of drug effects and safety throughout.

Researchers are evaluating the combination of baxdrostat and dapagliflozin in people with chronic kidney disease CKD and high blood pressure hypertension. This Phase III, double-blind, placebo-controlled study aims to assess whether this combination reduces the risk of serious kidney damage, heart failure events, or cardiovascular death compared to dapagliflozin alone. The study includes participants with CKD and hypertension who meet specific kidney function and blood pressure criteria. Participants who are not already taking SGLT2 inhibitors will first complete a 4-week dapagliflozin run-in period. Then, they will be randomly assigned to receive either baxdrostat plus dapagliflozin or a placebo plus dapagliflozin. Baxdrostat dosing may start low and be increased if needed. Study visits will occur at 2, 4, 8, 16, 34, and 52 weeks after randomization, and then approximately every four months until the study ends, which is based on the number of key kidney or heart-related events. Throughout the study, participants will have regular assessments including blood tests to monitor kidney function and potassium levels, blood pressure measurements, and evaluations of heart and kidney health. If participants stop the blinded study drug early, they will continue dapagliflozin if possible and remain in the study for ongoing visits and monitoring. The main outcome is whether the combination treatment reduces the risk of a 50% sustained decline in kidney function, kidney failure, heart failure events, or cardiovascular death over up to 37 months.

The trial investigates the use of the Adaptive Tip Catheter ATC as a first-line direct aspiration device for mechanical thrombectomy in patients experiencing an acute ischemic stroke in the anterior circulation. It aims to evaluate both the safety and effectiveness of this catheter in treating this serious condition. Participants will undergo mechanical thrombectomy using the ATC alone, attempting to remove the clot within the first three passes or until successful reperfusion is achieved if fewer passes are needed. After the procedure, patients will be monitored for 90 days to assess recovery and outcomes related to stroke treatment. During the study, researchers will assess reperfusion success through imaging, focusing on the third pass and overall procedure results. They will also monitor clinical outcomes such as functional independence measured by the Modified Rankin Scale, vessel damage, mortality, and any symptomatic brain bleeding. Follow-up evaluations occur up to 90 days post-procedure to gather these safety and effectiveness data.