Vannes

Researchers are studying patients with metastatic colorectal cancer (mCRC) who have a specific BRAFV600E mutation. This rare subtype of mCRC has poor prognosis and resistance to current treatments, especially in tumors with microsatellite stability or proficient mismatch repair. The study aims to collect detailed clinical data and biological samples to better understand treatment outcomes, resistance, and survival in real-world settings. Participants will provide blood samples and tumor tissue samples to support various research goals. The study will evaluate circulating tumor DNA during different lines of metastatic treatment to predict treatment response and resistance. It will also analyze the immune environment of BRAFV600E mCRC tumors and study specific subgroups with mismatch repair deficiencies. Clinical management data will be collected to inform future therapeutic approaches. During the study, patients will be monitored regularly with blood sample collections of 30 mL at each time point. Researchers will gather information about treatments, survival, and biological markers over time. The main outcome measured is overall survival from diagnosis up to five years. Patients must be able to comply with study procedures and provide informed consent. The study aims to improve knowledge of this aggressive cancer subtype and support development of new treatments.

Researchers are creating a national, prospective cohort to study children with idiopathic nephrotic syndrome (INS), a rare kidney disease. The goal is to collect detailed data on patients treated in pediatric nephrology centers across France, Reunion Island, Mayotte, and eventually other French overseas territories. This structured follow-up aims to better understand the disease's characteristics and provide a foundation for future clinical trials. The study involves enrolling pediatric patients diagnosed with INS and systematically collecting clinical, biological, psychological, and social data. Biological samples such as blood, urine, hair, and nails will be gathered at disease onset before immunosuppressive treatment begins. Data will be recorded through medical records from hospital visits and consultations, supplemented by annual telephone interviews for patients without active disease. Quality of life, treatment adherence, and aesthetic impact questionnaires will also be collected and integrated into a secure database. Participants will be followed over at least two years, with data collected regularly by clinical research staff. This includes medical validation of clinical information, annual telephone follow-ups, and questionnaire assessments. The study's primary outcome is the number and characteristics of included cases over two years. This ongoing monitoring will support future nested studies and improve understanding of pediatric INS outcomes and management.

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 the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.

Multiple myeloma is a type of cancer that affects plasma cells in the blood, often found in bones and bone marrow. It can cause symptoms like bone pain, fractures, infections, weaker bones, and kidney problems. This research evaluates the effects and safety of a new drug called Etentamig in adults with newly diagnosed multiple myeloma who are not eligible for transplant. The study includes two phases, phase 2 and phase 3, involving about 660 participants worldwide to assess adverse events, disease activity changes, and drug behavior in the body. In phase 2, participants receive one of three doses of Etentamig through intravenous infusions combined with subcutaneous injections of Daratumumab. In phase 3, participants receive the recommended phase 3 dose of Etentamig intravenously with Daratumumab injections, or a combination of Daratumumab injections, oral Lenalidomide capsules, and oral or intravenous Dexamethasone tablets/injections (DRd). The entire study may last up to approximately 16 years, with different treatment arms exploring these combinations. Participants will visit hospitals or clinics regularly for medical check-ups, blood tests, side effect monitoring, and questionnaires. Researchers will track the percentage of participants experiencing adverse events, changes in disease activity, minimal residual disease negative complete response rates, and progression-free survival over time. The study aims to understand the long-term effects and safety of these treatments in managing multiple myeloma in adults.

Researchers are evaluating the clinical effectiveness and safety of two antibiotic treatments, amoxicillin alone versus amoxicillin/clavulanate, for community-acquired pneumonia (CAP) in patients aged 65 years or older who are hospitalized in non-intensive care unit (ICU) wards. The study addresses an important public health concern about reducing inappropriate antibiotic use, especially since broad-spectrum antibiotics may cause side effects and contribute to antibiotic resistance. This Phase 3 trial aims to fill the evidence gap on the best antibiotic choice for older adults with CAP by directly comparing these two treatments. Participants will be randomly assigned to receive either intravenous or oral amoxicillin or amoxicillin/clavulanate for five days. The amoxicillin group will take 500 mg capsules three times daily or 1 g intravenously every eight hours. The amoxicillin/clavulanate group will receive two tablets of 500 mg/62.5 mg orally every eight hours or 1 g/200 mg intravenously every eight hours. Both regimens are approved for respiratory infections, and the study will assess clinical outcomes at 30 days after starting treatment to determine if amoxicillin alone is not worse than the combination therapy. During the study, participants will be monitored for clinical signs and safety outcomes up to 30 days after inclusion. Researchers will evaluate the patients' clinical response to treatment and any side effects. The trial involves multiple centers and includes follow-up calls or contacts to ensure adherence and collect necessary data. This study will provide important information to guide future treatment guidelines for older adults hospitalized with CAP.

Researchers are studying the biological features of advanced ALK-rearranged non-small cell lung cancer (NSCLC) in patients treated with new generation tyrosine kinase inhibitors (TKIs) as their first therapy. This study is part of the national EXPLORE ALK cohort, a multi-center observational project in France, focusing on patients with this specific genetic alteration. The goal is to better understand the tumor biology and resistance mechanisms by analyzing samples from diagnosis through disease progression. The study collects tumor tissue samples at diagnosis and, when possible, at disease progression for RNA sequencing to identify ALK fusion partners, variants, and co-mutations. Blood samples are also taken at diagnosis, first tumor evaluation, and at progression to analyze circulating tumor DNA (ctDNA) using next-generation sequencing panels that detect mutations, fusions, and other genetic changes. These biological analyses are centralized at specialized centers such as the Léon Bérard Center and Rouen University Hospital. Patients are treated with approved ALK inhibitors like alectinib, brigatinib, lorlatinib, or entrectinib as part of their standard care. Participants will provide blood samples at multiple time points and, if possible, tumor biopsy samples for detailed genetic analysis. Researchers will monitor the progression-free survival from treatment start for up to 72 months. The study involves regular evaluations to assess tumor status and collect biological material to track genetic changes over time. Consent for sample collection and participation in the study is required, and patient data is managed within the national health system framework.

Researchers are evaluating the effectiveness and safety of lorlatinib in patients with untreated ALK-positive non-small-cell lung carcinoma (NSCLC) in a real-world French context. The study focuses on adults aged 18 years or older who have locally advanced or metastatic ALK-positive NSCLC confirmed by specific diagnostic methods. This non-interventional study aims to understand how lorlatinib performs outside of controlled clinical trial settings. Participants will receive lorlatinib as the treatment for ALK-positive NSCLC. Before starting treatment, patients must undergo a complete radiological assessment including contrast-enhanced CT scans of the thorax and upper abdomen and brain MRI, as per routine care. The study monitors patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, reflecting their ability to carry out daily activities. During the study, researchers will assess progression-free survival from the start of treatment up to 25 months. Patients will be followed through scheduled visits and examinations, including evaluations of clinical status and safety monitoring. Participants are expected to comply with the study protocol throughout the observation period, and data will be collected according to standard care practices in a real-world setting.

Researchers are evaluating the effectiveness of different antimicrobial treatments for infections caused by difficult-to-treat Pseudomonas aeruginosa bacteria. This infection is especially challenging for patients who are critically ill or have weakened immune systems. The study focuses on comparing new beta-lactam/beta-lactamase inhibitor combinations, cefiderocol, and older drugs like aminoglycosides and colistin in real-life clinical settings across multiple hospital centers in France. Participants will receive intravenous antimicrobial therapy tailored to treat their difficult-to-treat P. aeruginosa infection. The study observes the use of new and older antimicrobial drugs to assess their clinical efficacy. Patient data and bacterial samples will be collected and analyzed centrally to better understand drug resistance mechanisms and treatment outcomes. Participants will be monitored for clinical cure shortly after completing therapy and on Day 7 ± 2 days. Researchers will collect clinical information through electronic case-report forms and send bacterial isolates to a national center for detailed testing. Outcomes include cure rates, resistance development, adverse events, and mortality rates, with follow-up during hospitalization and up to 28 days after treatment. The study aims to provide valuable real-world data on treating these challenging infections.

Researchers are studying Philadelphia-negative myeloproliferative neoplasms (MPN), which include Polycythemia Vera (PV), essential thrombocythemia (ET), and prefibrotic myelofibrosis (PreMF). These chronic blood cancers involve specific mutations like JAK2V617F and carry a high risk of blood clots that can cause serious health problems. Current treatments include low-dose aspirin to reduce arterial clots, but patients still face risks of thrombosis and bleeding. This trial explores whether direct oral anticoagulants (DOACs), such as Apixaban or Rivaroxaban, might better prevent these clotting events in patients with the JAK2V617F mutation. Participants will be randomly assigned to receive either a DOAC (Apixaban 2.5 mg twice daily or Rivaroxaban 10 mg once daily) or low-dose aspirin (100 mg once daily). The study focuses on high-risk MPN patients with JAK2V617F mutation and will compare the effectiveness and safety of DOACs versus aspirin for preventing blood clots. Treatment will continue with close monitoring throughout the study. During the study, researchers will track the time until any arterial or venous blood clots occur over a 24-month follow-up period. Participants will undergo regular assessments to monitor clotting events, bleeding risks, and overall health. The trial aims to gather detailed information on how well these treatments prevent thrombosis and their safety profiles, helping to guide future care for patients with these blood disorders.