Uden

Researchers are evaluating the safety and effectiveness of tulisokibart, a humanized monoclonal antibody, in people with moderately to severely active Crohn's disease. The research includes two studies: Study 1, which has induction and maintenance treatment phases, and Study 2, which only includes induction treatment. The main goals are to see if tulisokibart can help participants achieve clinical remission and endoscopic response compared to placebo, measured at 12 and 52 weeks depending on the study and region (US/FDA or EU/EMA).

Patients in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) with non-metastatic colon cancer that gave consent for additional blood withdrawals are enrolled in the observational PLCRC-MEDOCC substudy. In this study, blood is collected before surgery, after surgery and during follow-up. Within PLCRC-MEDOCC, patients with stage II colon cancer that are not considered to have an indication for adjuvant chemotherapy, can be included in the MEDOCC-CrEATE subcohort under the condition that they gave informed consent in PLCRC for biobanking of tissue and for future studies (Trial within Cohorts design). Patients included in MEDOCC-CrEATE will be randomized 1:1 to the (A) ctDNA-based treatment group versus (B) the standard of care group. A total of 1320 patients will be randomized. Patients randomized to the ctDNA-based treatment group will have their post-surgery samples analysed directly after informed consent for MEDOCC-CrEATE. All patients with detectable ctDNA will be offered adjuvant chemotherapy (3 months CAPOX). Patients with undetectable ctDNA will receive routine follow-up at the surgical department. The aim of this Trial within Cohorts study is to investigate how many patients with detectable ctDNA after surgery start with adjuvant chemotherapy.

Researchers are evaluating chemotherapy dosing strategies for older patients aged 70 years and above who have metastatic colorectal cancer and are candidates for palliative chemotherapy. This phase III, open-label, randomized controlled trial aims to compare upfront dose-reduced chemotherapy with standard full-dose chemotherapy to see if the reduced dose is not worse in terms of progression-free survival (PFS). The study also examines secondary outcomes including severe toxicity, quality of life, physical function, overall survival, treatment cycles, dose reductions, hospital admissions, cumulative dosage, and cost-effectiveness. Participants are classified based on their risk of chemotherapy toxicity using the Geriatric 8 (G8) questionnaire. Those at low risk are randomized to receive either full-dose or 25% dose-reduced doublet chemotherapy (a fluoropyrimidine combined with oxaliplatin). Patients at high risk receive either full-dose or dose-reduced monotherapy with a fluoropyrimidine. Targeted treatments like bevacizumab or EGFR inhibitors may be added. Dose adjustments are made for moderate kidney impairment. Treatments are given on schedules involving oral and intravenous chemotherapy drugs administered every 2 to 3 weeks. During the study, participants undergo assessments including clinical evaluations, laboratory tests to monitor blood counts and organ function, and questionnaires for quality of life and physical functioning. Progression-free survival is tracked for at least one year after randomization. Researchers closely monitor treatment toxicity, hospitalizations, dose modifications, and survival. The total planned enrollment is 587 patients, with follow-up for safety and effectiveness throughout the treatment period.

Researchers are evaluating the effectiveness and safety of obefazimod compared to a placebo in adults with moderately to severely active Crohn's Disease who have not responded well or are intolerant to conventional or advanced treatments. The study is a Phase 2b trial and includes three treatment phases: a 12-week Induction Phase, a 40-week Maintenance Phase, and a 48-week Extension Phase. The main goals are to assess how well obefazimod controls disease activity and its safety over these periods. Participants will receive either obefazimod or a matching placebo once daily, preferably in the morning with food. The trial includes an initial 12-week treatment to induce response, followed by a 40-week maintenance period to sustain results. Those who complete these phases may enter a 48-week Extension Phase to further evaluate the long-term safety and tolerability of obefazimod compared to placebo. During the study, participants will undergo regular assessments including clinical evaluations of disease activity using the Crohn's Disease Activity Index and endoscopic scoring at various time points up to week 52. Safety is monitored throughout, especially during the Extension Phase with checks for adverse events, blood tests, and other laboratory evaluations at scheduled visits. Overall, participation may last over a year, with careful monitoring of treatment effects and safety.

Researchers are investigating the treatment of multiple myeloma using a combination of medicines called daratumumab-lenalidomide-dexamethasone (Dara-Rd). This standard treatment in the Netherlands often suppresses the disease for a long time and continues until it stops being effective. The study aims to find out if stopping treatment temporarily, compared to continuing it without breaks, can improve quality of life by reducing side effects and allowing recovery from toxicity, without reducing survival time. The study involves patients who have completed 12 cycles of Dara-Rd treatment and have responded with at least a partial response without biochemical progression. These patients will be randomly assigned to either continue Dara-Rd treatment continuously or take a treatment-free interval. The medications involved include daratumumab injections, lenalidomide capsules, and dexamethasone. Reduced dosing of lenalidomide is allowed but not below 5 mg, and prior dexamethasone dose changes are permitted. The trial is a nationwide, open-label, randomized Phase III study. Participants will be followed for up to approximately 57 months to compare event-free survival and up to 69 months to compare progression-free survival after randomization. Researchers will monitor disease status, side effects, and overall health during this time. Patients must provide informed consent and will undergo regular assessments to evaluate the impact of continuous versus interrupted therapy on their disease and quality of life.

Researchers are evaluating the use of a Bayesian network model called ENDORISK to improve preoperative risk assessment of lymph node metastasis in patients with early stage endometrial cancer. The study aims to see if using ENDORISK in daily clinical practice enhances risk stratification compared to standard care. This includes assessing patient decisions about lymph node evaluation and shared decision-making between patients and doctors. Participants receive personalized risk assessments for lymph node metastases using the ENDORISK model. Treatment plans, including hysterectomy with bilateral salpingo-oophorectomy and possible lymph node surgery, are tailored based on this risk. The study is conducted in two oncology regions using a stepped wedge design with one-year intervals between implementation phases. During the study, patients complete digital or paper questionnaires to evaluate preoperative information and shared decision-making outcomes. Researchers track the proportion of patients undergoing lymph node staging, positive predictive value for lymph node metastases, survival rates, quality of life, experiences with the ENDORISK model, and regional care costs. Follow-up continues up to 12 weeks post-operation to assess these outcomes.

Researchers are comparing two diagnostic approaches for patients suspected of having muscle-invasive bladder cancer. The study evaluates progression-free survival over two years, the time to definitive treatment, and cost-effectiveness between the standard care method of transurethral resection of the bladder tumor (TURBT) and a newer approach using multi-parametric MRI (mpMRI) followed by a same-day cystoscopic bladder biopsy. This is a two-arm multicenter randomized controlled trial aiming to improve local staging methods for this condition. Participants will be randomly assigned to one of two groups. One group will receive the standard of care involving TURBT along with blood samples taken shortly before and after the procedure. The other group will undergo mpMRI followed by a cystoscopic bladder biopsy on the same day. These procedures are designed to assess and diagnose the suspected muscle-invasive bladder cancer more precisely. During the study, participants will be monitored for progression-free survival for up to two years. Researchers will collect data on how long patients remain free from disease progression, the timing of definitive treatments, and overall cost-effectiveness. The trial involves multiple centers, and participants will provide written informed consent before enrollment. This study focuses on adults suspected of muscle-invasive bladder cancer without evidence of lymph node or distant metastases.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are evaluating trastuzumab deruxtecan (T-DXd) in adults with unresectable or metastatic breast cancer that is either HER2-low or HER2 IHC 0. This includes patients with hormone receptor-negative or hormone receptor-positive cancer. The study aims to assess the safety and effectiveness of T-DXd by measuring the time patients benefit from the treatment before needing another anticancer therapy. Participants receive T-DXd through an intravenous infusion at a dose of 5.4 mg/kg on the first day of each 21-day cycle. Treatment continues until the disease progresses based on imaging, unacceptable side effects occur, other reasons for stopping arise, or for up to two years after the first dose. The study is open-label, multicenter, and global, focusing on patients who have not previously received anti-HER2 therapy for metastatic disease. During the study, researchers will monitor participants regularly with imaging scans to measure disease progression and collect biopsies. They will also assess heart function, organ health, and overall clinical status. The main outcome is the time from starting T-DXd to the start of the next anticancer treatment or death, followed for up to 24 months. Safety and side effects will be closely observed throughout the study.