Hoofddorp

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 evaluating the safety and effectiveness of bomedemstat (MK-3543) compared with the best available therapy (BAT) in adults with essential thrombocythemia (ET) who have not responded well to or cannot tolerate hydroxyurea. This phase 3 clinical trial aims to determine if bomedemstat provides a better durable clinicohematologic response in these participants. Participants will receive either bomedemstat as an oral capsule or one of the best available therapies, including anagrelide (oral capsule), busulfan (oral tablet), interferon alfa or its pegylated forms (subcutaneous solution), or ruxolitinib (oral tablet). The study involves a randomized, open-label design where treatments are compared directly. Throughout the study, participants will be monitored for their hematologic response up to about 52 weeks. Assessments include platelet and neutrophil counts before starting treatment to ensure eligibility. Safety and efficacy are tracked to evaluate the long-term impact of the treatments on ET.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are evaluating overall survival in men with metastatic castration-resistant prostate cancer (mCRPC), a form of prostate cancer that has spread beyond the prostate and no longer responds to hormone therapies. This Phase 3 randomized trial compares pasritamig (JNJ-78278343), a T cell redirecting agent targeting human kallikrein 2, combined with best supportive care (BSC), against placebo with BSC to understand the length of time participants survive from the start of treatment. Participants receive pasritamig or placebo through intravenous infusion along with best supportive care, which is provided at the treating physician's discretion. The study focuses on men who have previously undergone multiple prostate cancer treatments including androgen-receptor pathway inhibitors, taxane chemotherapy, radioligand therapy, and possibly PARP inhibitors. Patients must continue ongoing hormone therapy during the treatment phase. During the study, participants are monitored for overall survival up to 2 years and 8 months. Assessments include clinical evaluations and laboratory tests to measure kidney and liver function, blood counts, and general health status. Safety and treatment effects are closely observed, with eligibility based on performance status and organ function. The trial aims to provide detailed long-term outcome data for this advanced prostate cancer treatment approach.

Researchers are evaluating the effectiveness of selinexor in people with myelofibrosis (MF) who have not previously been treated with JAK inhibitors and who have normal or mildly to moderately low platelet counts. The study focuses on measuring the reduction in spleen size (spleen volume reduction) after 24 weeks of treatment. Additional safety and effectiveness outcomes will also be studied during the trial. Participants will receive oral selinexor tablets once a week at doses of either 60 mg or 40 mg. The study includes monitoring for response and safety over at least 24 weeks. Other drugs listed, such as ruxolitinib, pacritinib, and momelotinib, are noted but selinexor monotherapy is the main treatment being studied. Bone marrow biopsies and symptom assessments using a daily symptom diary will be part of the study procedures. During the study, participants will undergo imaging scans such as MRI or CT to measure spleen size and have blood tests to monitor blood counts and organ function. Researchers will assess symptom changes daily using a symptom assessment form. The primary outcome is the proportion of participants showing a significant spleen size reduction at week 24. Safety will be closely monitored, and participants must complete symptom diaries throughout the study, which will last at least 24 weeks.

This research aims to evaluate the impact of dupilumab compared to placebo on airway inflammation, airway resistance, and airway remodeling in people aged 40 to 85 years with chronic obstructive pulmonary disease (COPD). The study focuses particularly on mucus plugging and how it relates to lung function, exacerbations, and quality of life improvements. This is a multinational, randomized, double-blind, placebo-controlled Phase 4 study with two treatment groups. Participants will receive either dupilumab or a placebo, both given as subcutaneous injections. The treatment period lasts up to 24 weeks, within a total study duration of up to 40 weeks. The study includes 9 visits throughout this time to monitor progress and safety. During participation, researchers will assess lung mucus using imaging scores from baseline through Week 24 to measure changes. Other evaluations include lung function tests, monitoring exacerbations, and quality of life measures. Safety and effectiveness will be carefully tracked through these visits, with ongoing assessments to understand the treatment impact over the study period.

Researchers are investigating how exercise affects patients with metastatic colorectal cancer receiving chemotherapy. The study explores whether exercise can prevent chemotherapy dose changes caused by treatment side effects, improve immune function, and ultimately enhance progression-free survival. The trial also seeks to determine the best type and dose of exercise to recommend, as current evidence on optimal exercise prescription is limited. Using a Bayesian adaptive design allows for more efficient evaluation by potentially dropping less effective exercise programs early. Participants will be randomly assigned to one of three groups: resistance exercise, aerobic interval exercise, or usual care without a specific exercise program. The exercise interventions involve continuous aerobic and resistance exercises or continuous aerobic and aerobic interval exercises. These programs aim to reduce chemotherapy toxicity and improve psychological and physical strength. The study uses a multi-arm multi-stage design with interim analyses to select the most beneficial exercise prescription while minimizing patient exposure to less effective treatments. Throughout the study, participants will be monitored for chemotherapy dose modifications and progression-free survival for up to two years. Assessments include tracking chemotherapy dose adjustments during treatment cycles, immune function by evaluating natural killer cells, and quality of life measures. Researchers will also observe treatment-related toxicities and hospitalizations. The trial aims to provide evidence on how exercise can support chemotherapy effectiveness and improve outcomes in metastatic colorectal cancer patients.

Researchers are evaluating the safety and effectiveness of combining JSB462 (luxdegalutamide) at doses of 100 mg and 300 mg once daily with abiraterone, compared to an androgen receptor pathway inhibitor (ARPI) such as abiraterone or enzalutamide in adult men with metastatic hormone-sensitive prostate cancer (mHSPC). This Phase II study aims to select the recommended dose of the combination for further Phase III trials by assessing overall efficacy, safety, tolerability, and pharmacokinetics in participants. Participants receive JSB462 orally every day at either 100 mg or 300 mg doses continuously from randomization until disease progression, unacceptable side effects, death, or decision to stop treatment. Alongside this, abiraterone (1000 mg daily) or enzalutamide (160 mg daily) is also given continuously under the same conditions. The study includes a 28-day screening period, followed by the treatment period and then a 30-day post-treatment safety follow-up. After this, a long-term follow-up phase collects ongoing safety, efficacy, and survival data until the study ends. Throughout the study, participants undergo monitoring for prostate specific antigen (PSA) response, adverse events, dose adjustments, and duration of treatment exposure. Safety visits occur 30 days after treatment stops, and long-term follow-up tracks participant health until study completion. The total participation duration varies depending on individual treatment response and follow-up schedules, with assessments continuing for up to approximately 75 months from randomization.

Researchers are evaluating two types of cognitive-behavioral therapy (CBT) for adults aged 18 and older with anxiety-related disorders, including panic disorder, agoraphobia, generalized anxiety disorder, social anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder, and health anxiety disorder. The study aims to determine whether brief-intensive CBT leads to faster and better improvement in daily functioning such as work and family life compared to regular weekly CBT. This is a parallel-group randomized controlled trial conducted in multiple centers. Participants will receive either brief-intensive CBT, consisting of 16 exposure therapy sessions delivered over 4 half-days within 2 weeks plus 4 follow-up sessions within 3 months, or regular CBT consisting of 20 weekly sessions over 6 months. Both treatment approaches include 20 sessions of 45 minutes each and can be personalized to focus on improving work or family functioning. This trial compares the effects and feasibility of these two treatment schedules. During the 1-year study, participants will complete seven assessments lasting about 5 hours total, including online questionnaires and telephone interviews. These will evaluate health, disability, quality of life, anxiety and depression symptoms, coping strategies, and therapy expectations. The main outcome is the change in health and disability over 6 months. Additional measures include treatment effectiveness after 1 year, cost-effectiveness, and participants' preferences and drop-out rates.