Breda

Researchers are evaluating a "wait-and-see" approach for patients with rectal cancer who respond completely to neoadjuvant chemoradiotherapy. This study aims to provide both short-term and long-term data on cancer control and patient function when surgery is avoided in good responders. The research also seeks to establish a national network of expert centers to improve organ-preserving care and create a registry to gather more evidence about this treatment strategy. The standard treatment for locally advanced rectal cancer typically involves chemoradiotherapy followed by surgery. In this study, patients who show a complete clinical response after treatment will be observed without immediate surgery under a "wait-and-see" policy. The study is a multicenter prospective observational cohort and implementation study, focusing on patients aged 18 or older who have had a long course of chemoradiotherapy or a short course with a long waiting interval. The main goal is to track disease-free survival without tumor regrowth over two years. Participants will be closely monitored using clinical exams, endoscopy, and advanced MRI scans to confirm their response and detect any regrowth early. Researchers will measure outcomes such as two-year disease-free survival, regrowth rate, local control, overall survival, quality of life, and the ability of centers to provide high-quality organ preservation care. Patients will undergo intensive follow-up to ensure safety and gather comprehensive data on the effects of this less invasive approach over time.

Researchers are studying whether combining calderasib, a targeted therapy for the KRAS G12C mutation, with subcutaneous pembrolizumab can treat non-small cell lung cancer (NSCLC). The study aims to determine if people receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a phase 3, randomized, open-label, multicenter clinical trial focusing on participants with advanced or metastatic nonsquamous NSCLC carrying the KRAS G12C mutation. Participants will receive one of two treatment combinations. One group will take calderasib orally along with subcutaneous pembrolizumab and berahyaluronidase alfa injections. The other group will receive subcutaneous pembrolizumab combined with chemotherapy drugs pemetrexed and a platinum-based drug, either carboplatin or cisplatin, administered by intravenous infusion. These treatments are given as first-line therapy, and the study evaluates their safety and effectiveness. During the study, researchers will monitor participants for progression-free survival, especially focusing on those with at least 1% PD-L1 tumor proportion score, for up to approximately 48 months. Participants will undergo regular assessments to track cancer progression and response to treatment. Safety and efficacy data will be collected throughout the study to understand how well the treatments work and their side effects over time.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Physical restraints are still frequently used in about 20-25% of adult ICU patients in the Netherlands who are agitated or expected to become agitated, despite their harmful short- and long-term effects. This research evaluates the effectiveness of a person-centered multicomponent intervention (MCI) program that combines non-drug approaches with goal-directed light sedation using dexmedetomidine. The study compares this new approach with the traditional standard care that includes physical restraints, aiming to improve patient safety and outcomes during ICU stays. The intervention group will receive the MCI program, which involves non-pharmacological strategies and light sedation with dexmedetomidine as needed to manage agitation. This is compared against the current standard care involving physical restraints. The study focuses on adult ICU patients expected to stay longer than 24 hours and who show or are expected to show agitation within the first 14 days of ICU admission. The trial monitors short- and long-term outcomes as well as healthcare costs. Participants' involvement includes monitoring ICU-free days over 28 days as a primary outcome. Researchers will assess agitation levels, sedation needs, and the use of physical restraints. Safety and long-term effects will be tracked, with consent required for extended follow-up in related studies. The study excludes patients with certain neurological conditions, substance intoxication, or other risks, and requires participants or their relatives to understand Dutch for follow-up communication.

This research aims to evaluate the safety and effectiveness of BMS-986504, a selective PRMT5 inhibitor, when combined with Nab-paclitaxel and Gemcitabine, compared to a placebo combined with Nab-paclitaxel and Gemcitabine. The study focuses on participants with untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC) who have a specific genetic alteration called homozygous MTAP deletion. This is a randomized Phase 2/3 trial designed to explore treatment options for this patient population. Participants will be assigned to receive either BMS-986504 at specified doses on certain days along with Nab-paclitaxel and Gemcitabine, or a placebo with the same chemotherapy drugs. The treatments are given according to protocol schedules. Some participants may have received up to one cycle of Nab-paclitaxel and Gemcitabine before starting the study treatment, provided they did not experience disease progression or intolerable side effects. The initial cycle must be completed before randomization. During the study, researchers will monitor participants for progression-free survival and overall survival for up to three years after the last participant is randomized. Assessments include measuring tumor response using established criteria (RECIST v1.1). Participants will undergo evaluations to track safety, treatment effects, and disease status throughout the trial period.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

Researchers are evaluating sacituzumab tirumotecan alone and combined with pembrolizumab compared to the treatment chosen by a physician for people with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer that cannot be removed by surgery or has spread to other parts of the body. This study focuses on participants whose cancer has progressed despite prior endocrine therapy, including treatment with a CDK4/6 inhibitor. The main goal is to see if these treatments improve progression-free survival, which means the length of time the cancer does not worsen, over up to approximately 38 months. Participants receive sacituzumab tirumotecan as an intravenous infusion, either alone or combined with intravenous pembrolizumab. The comparison group receives the treatment of physician's choice, which may include intravenous paclitaxel, nab-paclitaxel, liposomal doxorubicin, or oral capecitabine. The study is open-label and randomized, meaning participants are assigned to different treatment groups openly. Treatments are administered according to the study protocols, with ongoing monitoring during the treatment period. Throughout the study, participants are monitored regularly to assess their cancer status and overall health. This includes evaluations by blinded independent central review using RECIST 1.1 criteria to measure tumor progression. Researchers also assess safety, organ function, and performance status. The total participation time may last up to around 38 months to track progression-free survival and other outcomes. Careful monitoring helps ensure participant safety and collects data on treatment effectiveness and side effects.

Researchers are evaluating the safety and effectiveness of a new oral medicine called vepugratinib compared with a placebo in adults with advanced or metastatic urothelial carcinoma, a type of bladder cancer that has a specific FGFR3 genetic alteration. This Phase 3 study aims to see if vepugratinib combined with two other drugs, enfortumab vedotin (EV) and pembrolizumab, can improve treatment outcomes for people who have not received prior systemic therapy for their cancer. Participants will receive either vepugratinib or placebo taken orally alongside enfortumab vedotin and pembrolizumab, both administered by intravenous infusion. The study is randomized, double-blind, and placebo-controlled to ensure reliable comparison between the vepugratinib and placebo groups. Treatment and monitoring will continue for up to approximately 6 years, allowing long-term assessment of safety and treatment effects. During the study, participants will be regularly evaluated for treatment-related side effects, response rates, and how long the cancer remains controlled without progression. Researchers will use established criteria to measure tumor response and will conduct thorough safety monitoring over the entire study period. Participation may last up to six years, during which participants will undergo laboratory tests, imaging, and clinical assessments to track their health and treatment response.

Researchers are evaluating patient management strategies to improve weaning success from venoarterial extracorporeal membrane oxygenation (VA ECMO) support in adults with cardiogenic shock. This study, part of the REMAP ECMO platform, focuses on the effects of left ventricular (LV) unloading using an intra-aortic balloon pump (IABP) compared to VA ECMO alone. The aim is to fill knowledge gaps from current observational studies by conducting randomized embedded clinical trials assessing therapies already in use but lacking high-quality evidence. The study involves randomizing patients receiving VA ECMO support to either receive additional LV unloading with an IABP or VA ECMO alone. The IABP device is inserted percutaneously into the thoracic aorta to support the heart by synchronized balloon inflation and deflation. A nested physiological substudy at Erasmus Medical Center Rotterdam evaluates the effects of IABP on respiratory and hemodynamic parameters, including microcirculation, macrocirculation, and the use of positive end-expiratory pressure (PEEP) as an unloading method during a decremental PEEP trial. Participants will be monitored for outcomes including successful weaning from ECMO within 30 days and changes in end diastolic volume within 24 hours after ECMO initiation. Assessments involve blinded evaluations of physiological effects, respiratory and circulation measurements, and safety monitoring. The study collects data through a patient registry for ongoing quality monitoring and observational analyses alongside the embedded randomized trials.

Researchers are evaluating the safety and effectiveness of upadacitinib in treating adults and adolescents with moderate to severe hidradenitis suppurativa (HS) who have not responded to or cannot tolerate anti-tumor necrosis factor (TNF) therapy. HS is an inflammatory skin disease causing painful lesions in areas such as the underarms, groin, and anal/genital regions. This phase 3, double-blind study involves approximately 1328 participants worldwide and aims to monitor disease activity and adverse events over time. Participants will receive oral tablets of either upadacitinib or placebo once daily during Period 1 and Period 2, lasting a total of 36 weeks. In Period 1, participants are randomly assigned to one of two treatment groups, with a 50% chance of receiving placebo. Based on results and placement in earlier periods, participants enter Period 2 with six potential treatment groups. Eligible participants from these periods may continue into Period 3, a long-term extension lasting 68 weeks, continuing the same daily oral treatment. Following the treatment periods, participants will be followed for approximately 30 days. During the study, participants will attend regular outpatient visits for medical assessments, monitoring for side effects, and completing questionnaires. Researchers will measure the percentage of participants achieving a clinical response called HiSCR 50 from baseline to week 16 and track adverse events up to approximately week 108. The study may require a higher treatment commitment compared to usual care, but provides close monitoring of disease activity and safety throughout all study phases.