Utrecht

Researchers are evaluating the safety and appropriate dose of increasing levels of the radioactive drug 131I-TLX101, given by intravenous infusion, combined with the best standard care in adults newly diagnosed with glioblastoma, a type of brain cancer. This open-label, single-arm study is conducted across multiple centers and aims to understand how patients tolerate this treatment alongside standard therapies. Participants receive escalating doses of 131I-TLX101 through an intravenous infusion along with the standard chemoradiation therapy known as the Stupp regimen, beginning 3 to 6 weeks after surgical removal of the tumor. The study includes a dose-finding phase to establish the recommended dose, with safety monitored throughout. The radioactive drug is administered in ascending doses, and the study observes participants for up to 62 weeks. During the study, participants will undergo regular safety assessments including laboratory tests of liver and kidney function, monitoring for adverse events, and evaluations of treatment-related toxicities for up to 62 weeks. Researchers will track the incidence and severity of dose-limiting toxicities and treatment-emergent adverse events. Participants must comply with radiation safety guidelines and attend scheduled visits for monitoring. The total study duration from screening until the end is about 62 weeks.

The LuDO-N Trial is a phase II multi-center clinical study investigating the use of 177Lu-DOTATATE in children with recurrent or relapsed high-risk neuroblastoma. This trial aims to assess how well this treatment works by measuring the response at 1 and 4 months after treatment ends. Secondary goals include evaluating survival rates, treatment-related side effects, and examining how tumor characteristics relate to treatment response. Participants receive two doses of 177Lu-DOTATATE administered intravenously, with at least two weeks between doses. The first dose is based on the patients weight, while the second dose is adjusted using scans to control radiation exposure, particularly to avoid kidney toxicity. Patients must be prepared for autologous stem cell transplantation as part of this intensified treatment approach. During the study, participants will undergo various scans and laboratory tests before starting treatment and at scheduled times to monitor tumor response and side effects. Researchers will assess treatment effectiveness using established neuroblastoma response criteria and will follow patients for up to five years to monitor survival and any long-term effects. The total participation time includes treatment administration and extended follow-up for safety and outcomes.

Researchers are working to create and use a comprehensive database focused on intracranial aneurysms IA. This project collects and studies clinical history, imaging data, biological samples, and other information to understand factors linked to the formation and rupture of aneurysms. They aim to identify genetic, environmental, and anatomical markers, as well as evaluate outcomes from different treatment strategies and improve patient care protocols. Participants include patients with diagnosed aneurysms, both ruptured and unruptured, family members of affected individuals, and healthy volunteers. Data collected involves detailed clinical records, imaging scans like MRI angiography and CT angiography, and various biological samples such as blood, cerebrospinal fluid, saliva, and stool. Consent covers access to medical records, use of biological samples, and potential future research uses including genetic analyses. During the study, participants provide health and lifestyle information, imaging data, and biological samples. Researchers will monitor multiple long-term outcomes including disease progression, life expectancy, quality of life, neurological and cognitive status, and treatment effects over periods up to 20 years. Data confidentiality is maintained, and participants can withdraw at any time without affecting their medical care. The study aims to validate disease models and support advances in aneurysm management and research.

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 studying a new type of scan called FAPI-PETCT to see how well it detects metastases in patients with advanced gastric cancer. The study aims to find out if this scan can better identify cancer spread, leading to changes in treatment plans such as avoiding unnecessary surgeries or shifting to comfort-focused care. It also evaluates whether the scan causes less burden for patients compared to current methods. Participants will receive the standard care for gastric cancer and undergo one additional FAPI-PETCT scan, where a small amount of 18F-FAPI-74 is given intravenously about 60 minutes before a PETCT scan lasting around 20 minutes. The results from this scan will help doctors decide on further tests or surgery needed. The study monitors changes in diagnosis and treatment decisions based on the scan. During the study, participants will complete questionnaires taking about 4 hours total and spend approximately 2 hours for the extra scan. Researchers will measure outcomes such as changes in treatment intent, diagnostic work-up, scan accuracy, incidental findings, patient burden, quality of life, and safety over about one year. Follow-up includes quality of life assessments and cost evaluations at multiple time points after staging.

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

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 evaluating the effects of enicepatide, a dual GLP-1GIP receptor agonist, at multiple doses compared with placebo for weight management in adults with obesity or overweight who do not have Type 2 diabetes. This Phase III, randomized, double-blind study aims to assess both the efficacy and safety of once-weekly enicepatide in this population, addressing weight-related comorbidities such as prediabetes, hypertension, and cardiovascular conditions. Participants will be randomly assigned to receive either placebo or one of three enicepatide dosing regimens, administered once weekly via an integrated drug-device combination product. The treatment phase lasts through 72 weeks, during which changes in body weight and other health measures are monitored. The study includes multiple assessments to track body weight percentage change, waist circumference, fasting glucose and insulin levels, lipid profiles, blood pressure, and quality of life measures. Throughout the study, participants will undergo regular evaluations including physical examinations, laboratory tests, and questionnaires related to physical functioning and urinary incontinence. Researchers will monitor adverse events, patient-reported health questionnaires, and biomarkers at baseline and weekly intervals through week 72. This long-term follow-up allows for a comprehensive assessment of treatment effects and safety in participants managing obesity or overweight without Type 2 diabetes.

Researchers are evaluating the safety, effectiveness, and how the body processes and responds to NXT007 prophylaxis compared with emicizumab prophylaxis in people aged 12 years and older who have severe or moderate congenital hemophilia A without factor VIII FVIII inhibitors, or any severity of hemophilia A with FVIII inhibitors. This phase 3, randomized, open-label study aims to compare these treatments to better understand their impact on bleeding rates and treatment burden. Participants will be randomly assigned to one of two main treatment groups. One group will receive NXT007 prophylaxis administered subcutaneously using an integrated drug-device combination product. The other group will receive emicizumab prophylaxis via subcutaneous injections, starting with weekly loading doses for 4 weeks, then maintenance dosing at various intervals depending on prior treatment status. After the main treatment period, participants from both arms can continue or switch to NXT007 in an open-label extension phase. Throughout the study, participants will be closely monitored with regular assessments, including measuring annualized bleed rates for different types of bleeds, treatment burden questionnaires, and safety evaluations such as adverse event monitoring and laboratory tests. These evaluations will continue throughout approximately 3.5 years of study participation to provide comprehensive data on treatment effects and safety.

Researchers are evaluating the effectiveness, safety, and how the body processes and responds to NXT007 prophylaxis compared to Factor VIII FVIII prophylaxis in people aged 12 years and older with severe or moderate congenital hemophilia A who do not have inhibitors. This phase III study focuses on participants who have previously been treated with FVIII prophylaxis. The goal is to understand how NXT007 performs against the current standard treatment for this condition. Participants will be randomly assigned to receive either NXT007 prophylaxis, given as a subcutaneous injection with an integrated drug-device combination product, or standard Factor VIII prophylaxis according to local dosing and frequency guidelines. After the main six-month treatment period, those receiving NXT007 may continue this treatment in an open-label extension, and those initially on FVIII prophylaxis may switch to NXT007 during this extension phase. During the study, participants will be closely monitored through various assessments, including tracking the annualized bleed rate ABR for treated bleeds over six months, questionnaires evaluating treatment burden and impact on social and recreational activities, and safety evaluations such as adverse events, injection-site reactions, and antibody development against NXT007. The study will continue follow-up for approximately 3.5 years to gather comprehensive data on treatment effects and safety.