Assen

This trial studies men with low-volume, hormone-sensitive metastatic prostate cancer to evaluate if a shorter treatment duration with androgen receptor pathway inhibitors (ARPIs) like Apalutamide or Enzalutamide is as effective as continuous therapy. The purpose is to see if stopping ARPI treatment after 12 months, with the option to restart if the cancer progresses, can reduce side effects and costs without worsening outcomes. This is a Phase 3 randomized nationwide study focusing on patients with low-volume metastatic disease confirmed by imaging and clinical assessment. Participants will receive androgen deprivation therapy (ADT) combined with either continuous ARPI treatment or ARPI treatment stopped at 12 months. Those who stop ARPI after 12 months may restart treatment if their PSA levels rise, confirmed by a second test at least 4 weeks later. The study compares these two approaches to understand if shorter ARPI use is non-inferior to continuous use, aiming to reduce treatment toxicity while maintaining disease control. Participants will be followed for up to 6 years, with clinical progression-free survival as the main outcome. Researchers will monitor time from study inclusion to disease progression or treatment end. Patients will undergo regular assessments including PSA testing and clinical evaluations to track disease status. Safety and treatment effects will be closely observed throughout the study period, which includes up to 5 years of active follow-up after randomization.

Researchers are evaluating the effect of muvalaplin on reducing cardiovascular risk in adults with elevated lipoprotein(a) levels who either have atherosclerotic cardiovascular disease or are at risk for a heart attack or stroke. This Phase 3, randomized, double-blind, placebo-controlled study focuses on adults with high Lp(a) levels and prior or potential cardiovascular events. The study aims to assess the time to the first major adverse cardiovascular event over about 5.25 years. Participants will be randomly assigned to receive either muvalaplin or a placebo, both administered orally. The study includes individuals with Lp(a) levels of at least 175 nanomoles per liter who have had a prior cardiovascular event within 10 years or are at risk for a first event due to conditions such as coronary artery disease, carotid stenosis, peripheral artery disease, high coronary artery calcium score, reduced kidney function with diabetes, or other high-risk factors. The treatment period lasts through the study duration, with close monitoring. During the study, participants will be regularly evaluated to track the occurrence of major adverse cardiovascular events, including heart attacks and strokes. Safety assessments will monitor blood pressure, kidney function, and heart failure status among other health indicators. The primary outcome measures the time to the first major cardiovascular event from baseline up to the end of the study, which spans approximately 5.25 years.

Researchers are investigating whether cognitive remediation (CR) training can help people with severe mental illness (SMI) who need supported housing due to severe cognitive and daily living problems. The study also explores if combining CR training with mild brain stimulation called transcranial Direct Current Stimulation (tDCS) can improve the effects of CR training. This trial is designed to evaluate improvements in daily functioning, cognitive skills, and personal goal achievement in people with SMI who experience persistent challenges in multiple areas of life. Participants will receive 16 to 20 weeks of cognitive remediation training twice weekly using a program called CIRCuiTS, which focuses on improving cognitive and metacognitive skills and applying these skills in daily life. They will be randomly assigned to receive either active tDCS brain stimulation or sham (inactive) tDCS alongside the CR training. The brain stimulation is applied to promote neural plasticity during cognitive exercises by gently altering brain activity in key areas. The study uses a triple-blinded, sham-controlled design across multiple centers. Participants will be assessed at several points: baseline (16 weeks before treatment), pre-treatment, post-treatment (after 16 to 20 weeks of training), and 6 months after treatment ends. Evaluations include questionnaires on independent living skills, goal attainment, social functioning, and continuous monitoring using the Behapp application during the entire study period, which may last up to 16 months. Optional in-depth interviews will explore participants' experiences with the training and its impact on their cognition and daily life. The study aims to determine if CR alone or combined with tDCS can enhance recovery and be recommended for standard care in SMI.

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 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 studying the changes and characteristics of the gut microbiome during chemotherapy in patients with metastatic or irresectable colorectal cancer (CRC). The study aims to explore how the gut microbiome relates to the effects of chemotherapy, as current treatments have limited overall survival and significant side effects. Understanding the microbiome could help improve treatment selection and effectiveness for CRC patients undergoing systemic anti-tumor therapy. Participants will collect fecal samples at home before starting treatment and three months after treatment begins, coinciding with response evaluations. They will also fill out questionnaires about factors that might affect the microbiome, such as antibiotic or proton pump inhibitor use. Additionally, blood samples will be collected before treatment and three months later for storage and analysis. Treatments include any combination of chemotherapy with or without anti-VEGF or anti-EGFR therapy. During the study, researchers will monitor changes in the gut microbiome and evaluate the patients' response to chemotherapy over two years. Outcome measures include prediction of response to conventional systemic anti-tumor therapy. Participants must provide informed consent and comply with study procedures, including sample collection and questionnaires. The study focuses on improving understanding of the microbiome's role in treatment outcomes and safety in metastatic or irresectable CRC.

Researchers are evaluating treatments for men with high-risk non-metastatic prostate cancer to compare robot-assisted radical prostatectomy (RARP) and external beam radiotherapy (EBRT), which may be combined with androgen deprivation therapy (ADT). This study aims to understand which treatment better supports health-related quality of life, functional outcomes, cost-effectiveness, progression-free survival, and distant metastasis-free survival. Currently, there is no clear consensus on the optimal treatment, leading to varied use of these options across hospitals. The study examines these two common treatment methods for high-risk prostate cancer. Both RARP and EBRT (with or without ADT) have side effects that can affect patients' quality of life. By collecting detailed data on outcomes and costs, the study seeks to provide evidence to guide treatment choices and improve shared decision-making between patients and healthcare providers. Participants will be followed for at least three years after starting treatment. During this time, researchers will assess functional outcomes and health-related quality of life. These long-term measures will help determine how each treatment impacts patients over time, supporting better personalized care and informing national guidelines.

Researchers are evaluating a personalized lifestyle intervention tailored for patients with affective disorders, including bipolar disorder and severe depression, who face a higher risk of cardiovascular disease largely due to unhealthy lifestyles. This pilot study aims to assess the acceptability and feasibility of this new lifestyle program for outpatients treated in mental health care or general practice, focusing on improving physical health and quality of life. The intervention, called Lifestyle InterVEntion (LIVE), is based on the Coaching on Lifestyle (CooL) program and adapted to address challenges in motivation and self-management for depressed patients. It lasts six months and includes 13 weekly group sessions lasting 1.5 to 2 hours, plus five individual sessions involving a support person close to the patient. Each session incorporates positive psychology activities and physical exercise, followed by homework tasks. After the main intervention, two booster sessions occur at approximately two and six months. Participants will be monitored throughout the intervention and follow-up periods, with assessments including adherence, dropout rates, and qualitative interviews to evaluate feasibility and acceptability. The total observational period spans from September 2020 to November 2022, with specific outcome measurements at various time points up to 18 weeks. The study collects detailed feedback to understand how well the program fits the needs of patients with depression.

Researchers are studying patients diagnosed with colorectal cancer, small bowel cancer, and anal cancer to better understand factors that affect treatment outcomes and survival. This study looks beyond tumor stage to explore how biochemical, genetic, environmental, and clinical factors may influence tumor recurrence and patient survival. It aims to address the gap in knowledge caused by most cancer patients not participating in clinical trials, and to validate trial results in a broader patient population. This is a prospective observational cohort study where data is collected from patients starting at their primary diagnosis and continuing until death. After informed consent, researchers gather detailed information on medical history, clinical status, imaging, pathology, tumor characteristics, treatments, hospital stays, side effects, and adverse events. Additional consent allows collection of patient-reported outcomes on quality of life and work ability, as well as biological materials like blood and tumor tissue for research and biobanking. Participants will be closely followed over time with ongoing data collection on treatment effects, clinical outcomes, and patient experiences. The study aims to provide accurate real-world data on various treatments and outcomes and to serve as a resource for future research into prognostic markers, new therapies, molecular studies, and health care policy. The main outcome measured is progression-free survival, tracked for up to 10 years, to better understand long-term treatment impact.

Researchers are evaluating a new virtual reality (VR) therapy called VR-VOICES for people who hear distressing voices that others cannot hear, known as auditory verbal hallucinations (AVH). These symptoms often occur in psychiatric disorders and can be persistent and disabling despite medication. This randomized controlled trial compares VR-VOICES to usual treatment to see if it can reduce the distress and frequency of these voices, while also examining effects on clinical symptoms, quality of life, and healthcare costs. Participants with a psychiatric diagnosis who have experienced distressing AVH for at least 3 months and are 16 years or older will be randomly assigned to either the VR-VOICES intervention or treatment as usual (TAU). The VR-VOICES therapy involves 7 to 10 individual sessions, each lasting 45 to 60 minutes, plus two booster sessions. During therapy, participants create a virtual avatar representing the voice they hear and engage in dialogues with it, which are voiced by the therapist. Over time, the avatar becomes less hostile as participants gain control and resilience. The control group receives standard care including medication, counseling, and psychological support. Participants will be assessed at the start, during some VR sessions, after 12 weeks, and again at 6 months. Researchers will measure the severity of voices, their frequency, impact, beliefs about them, and related anxiety and distress using questionnaires and daily diaries. They will also evaluate overall clinical symptoms, quality of life, and the cost-effectiveness of the treatment. The primary outcome is the change in voice severity from baseline to after treatment at 3 months.