Vannes

Researchers are investigating metastatic colorectal cancer mCRC patients who have a specific genetic change called the BRAFV600E mutation. This rare subtype of mCRC often shows poor response to current treatments and has a generally poor outlook. The study aims to collect detailed clinical data and biological samples to better understand this condition, including how patients respond to treatments and what factors predict their survival. It focuses on real-world treatment outcomes and biological markers that might influence therapy choices and resistance. Participants will provide blood samples at multiple times during their treatment, including before and during the first three treatment cycles, at 3 and 6 months after starting each treatment line, and when disease progression occurs following certain therapies. The study gathers up to 390 mL of blood per participant over time to analyze circulating tumor DNA and immune environment factors. This observational approach will help researchers identify biomarkers related to treatment response and disease progression. During the study, participants clinical progress and survival will be tracked for up to five years. Researchers will review overall survival from diagnosis to death and assess how prognostic markers relate to progression-free survival and response to treatments. The study involves collecting tumor tissue samples and blood tests, along with routine follow-up visits. All data collected will contribute to understanding BRAFV600E mCRC and improving future treatment strategies.

Researchers are conducting a prospective, multicenter cohort study to follow children with idiopathic nephrotic syndrome INS, a rare kidney disease. The study aims to collect data on pediatric patients treated by pediatric nephrologists in France and its overseas territories to better understand the diseases characteristics and support future clinical trials. The study involves regularly recording medical, biological, psychological, and social data through routine clinical follow-ups, hospitalizations, and consultations. Additionally, annual telephone interviews will be conducted for patients in remission. Quality of life, treatment adherence, and treatment impact questionnaires will also be collected. A biobank is established to collect blood, urine, hair, and nail samples at the disease onset before immunosuppressive treatment begins. Participants will be followed from disease onset until age 18 or transfer to adult nephrology care. Data is collected via a secure website, medically validated and entered by clinical research staff. The main outcome is the number of cases included and their characteristics over two years. Participation involves routine care visits, interviews, and questionnaires, with continued monitoring planned through the study period ending in 2048.

Researchers are evaluating the efficacy and safety of the combination of divarasib and pembrolizumab compared with pembrolizumab combined with pemetrexed and either carboplatin or cisplatin. This study focuses on adults with previously untreated, advanced or metastatic non-squamous non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The goal is to assess these treatments as first-line options in this specific lung cancer population. Participants will be randomly assigned to one of two groups. One group will take divarasib orally once daily and receive pembrolizumab through an intravenous infusion every three weeks. The other group will receive pembrolizumab, pemetrexed, and either carboplatin or cisplatin via intravenous infusions every three weeks. Treatment continues with these schedules, following the study protocol for up to approximately five years of follow-up. During the study, participants will have regular assessments to monitor their health and response to treatment. These include imaging and clinical evaluations to measure progression-free survival and overall survival for up to five years. Researchers will also track quality of life, symptom changes, treatment side effects, and adverse events using questionnaires and patient-reported outcomes. Safety monitoring and detailed evaluations will help understand the effects of the treatments over the study duration.

Researchers are evaluating the effects of a triple therapy inhaler combining budesonide, glycopyrronium, and formoterol fumarate BGF MDI 32014.49.6 g compared to a dual therapy inhaler with glycopyrronium and formoterol fumarate GFF MDI 14.49.6 g on heart and lung outcomes in adults with Chronic Obstructive Pulmonary Disease COPD who have a higher risk for heart and lung events. This Phase III study is randomized, double-blind, and conducted at multiple centers, focusing on participants with COPD and elevated cardiopulmonary risk. Participants will receive either the triple therapy inhaler or the dual therapy inhaler, both administered twice daily. The study compares these two inhalers over a period of up to three years, monitoring for serious cardiac or COPD events. The trial includes careful evaluation of various heart and lung-related health events during this period. During the study, participants will be closely monitored through regular visits, assessments, and tests to measure lung function, heart events, and COPD exacerbations. Researchers will track the time until the first severe cardiac or COPD event and evaluate other cardiovascular and respiratory outcomes over up to three years. Participants will also be assessed for their ability to properly use the inhaler and adherence to the study protocol throughout the trial.

Multiple myeloma MM is a cancer affecting plasma cells in the blood, often found in bones and bone marrow. It can cause bone pain, fractures, infections, weaker bones, and kidney failure. Researchers are studying the investigational drug Etentamig to understand its side effects, impact on disease activity, and how it behaves in the body for adults with MM. This study is conducted in two phases, phase 2 and phase 3, involving about 660 adult participants worldwide who have newly diagnosed MM and are not eligible for transplant. In phase 2, participants receive one of three doses of Etentamig combined with daratumumab in phase 3, participants receive the recommended phase 3 dose RP3D of Etentamig with daratumumab or a combination of daratumumab, lenalidomide, and dexamethasone DRd. Etentamig is given as intravenous infusions, daratumumab as subcutaneous injections, lenalidomide as capsules, and dexamethasone as oral tablets or intravenous injections. The study lasts approximately 16 years, with treatments continuing until the recommended dose is reached or as part of the study duration. Participants will attend regular hospital or clinic visits where their response to treatment will be monitored through medical exams, blood tests, side effect checks, and questionnaires. Researchers will measure outcomes like adverse events, disease activity changes, minimal residual disease rates, progression-free survival, and overall survival over up to 16 years. The study aims to assess both safety and disease control with ongoing monitoring and evaluations throughout the long study period.

Researchers are evaluating two antibiotic treatments for community-acquired pneumonia CAP in patients aged 65 years or older who are hospitalized in non-intensive care unit ICU wards. The study aims to compare the clinical effectiveness and safety of amoxicillin alone versus amoxicillin combined with clavulanate. This trial addresses an important gap in evidence about the best antibiotic choice for older adults with CAP, as current broad-spectrum antibiotic use is debated due to possible side effects and antibiotic resistance concerns. Participants will be randomly assigned to receive either amoxicillin or amoxicillinclavulanate for 5 days. Both medications are approved for treating respiratory infections and can be given orally or intravenously. Amoxicillin is given as 500 mg capsules or 1 g IV every 8 hours, while amoxicillinclavulanate is given as tablets containing 500 mg amoxicillin with 62.5 mg clavulanate or IV vials with 1 g amoxicillin and 200 mg clavulanate every 8 hours. This open-label, non-inferiority trial will compare outcomes at 30 days after treatment begins. During the study, participants will be monitored for clinical responses, cure rates, antibiotic treatment duration, hospital stay length, mortality, and adverse events related to antibiotics. Researchers will also track pneumonia recurrence, ICU transfers, and compliance with treatment. Follow-up assessments include clinical evaluations and laboratory tests up to 30 days after hospital admission. The study will provide important data to guide antibiotic use in older adults with CAP.

Researchers are studying advanced non-small cell lung cancer NSCLC with ALK gene rearrangement treated with next-generation tyrosine kinase inhibitors TKIs as first-line therapy. This prospective study, part of the national EXPLORE ALK cohort, aims to understand the biological characteristics and resistance mechanisms of this cancer type. It involves patients with stage IIIB or IV NSCLC who are not eligible for curative locoregional treatment and have confirmed ALK rearrangement. The study collects tumor tissue samples at diagnosis and at disease progression, if available, to analyze ALK fusion partners, variants, and co-mutations using RNA sequencing. Blood samples are taken at diagnosis, first tumor evaluation, and disease progression to analyze circulating tumor DNA ctDNA with next-generation sequencing. Treatments studied include alectinib, brigatinib, lorlatinib, and entrectinib, either marketed or under early access programs. Participants provide blood samples and allow use of tumor tissue for centralized biological analyses. Researchers measure progression-free survival up to 72 months as the primary outcome, along with overall survival, response rates, duration of response, ctDNA clearance, and resistance mechanisms associated with treatment and ALK fusion partners. The study involves regular evaluations over several years to monitor treatment outcomes and biological changes.

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. This study, sponsored by Pfizer, focuses on adults aged 18 years and older who have locally advanced or metastatic ALK-positive NSCLC confirmed by specific diagnostic tests. The goal is to understand how lorlatinib works and its safety profile outside of controlled clinical trial settings. Participants in this study receive lorlatinib as a single agent at a dose of 100 mg taken orally once daily without interruption. The treatment continues as per routine care, and patients undergo thorough radiological evaluations including contrast-enhanced CT scans of the thorax and upper abdomen, as well as brain MRI, before starting lorlatinib. The study monitors various outcomes such as progression-free survival, overall survival, response rates, duration of response, and adverse events over a period of up to 48 months. Throughout the study, participants will have scheduled assessments at regular intervals including clinical evaluations, imaging studies, and questionnaires to track symptoms, treatment adherence, and quality of life. Researchers will also monitor for specific side effects, treatment resistance mechanisms, and changes in patient-reported outcomes related to central nervous system toxicity and overall health status. The total duration of participation includes follow-up visits lasting up to 48 months to gather long-term data on treatment effects and safety.

Researchers are evaluating different antimicrobial therapies for infections caused by difficult-to-treat Pseudomonas aeruginosa, a type of bacteria resistant to many common antibiotics. This study focuses on comparing new beta-lactambeta-lactamase inhibitor combinations, cefiderocol, and older treatments like aminoglycosides and colistin to understand their effectiveness in real-life settings for patients facing these challenging infections. The study is a prospective, multicenter cohort involving patients who require intravenous antibiotic treatment for their P. aeruginosa infections. Participating patients will receive one of the available antimicrobial options, and their bacterial samples will be analyzed centrally to assess susceptibility and resistance mechanisms. The study collects clinical data throughout treatment and monitors outcomes such as cure rates, resistance development, adverse events, and mortality. Participants will be followed until hospital discharge and up to 28 days after treatment completion. Researchers will track clinical cures, microbiological eradication, adverse events, emergence of resistance, and acquisition of other multidrug-resistant bacteria. Data collection includes electronic case reports and laboratory testing on bacterial isolates. The total participation duration varies according to hospital stay and follow-up schedules, with rigorous monitoring of safety and treatment outcomes.

Philadelphia-negative myeloproliferative neoplasms MPNs such as Polycythemia Vera, Essential Thrombocythemia, and Prefibrotic Myelofibrosis are chronic blood cancers caused by mutations affecting blood cell growth. These diseases carry a high risk of blood clots, which can cause serious complications and death. Current treatments include low-dose aspirin, but blood clots still occur in some patients despite therapy. This trial aims to study whether direct oral anticoagulants DOACs, which have shown benefits in other cancer patients, might help prevent blood clots in MPN patients with a specific mutation called JAK2V617F. Participants will be randomly assigned to receive either a direct oral anticoagulanteither Apixaban 2.5 mg twice daily or Rivaroxaban 10 mg once dailyor low-dose aspirin 100 mg once daily. The choice of DOAC is up to the investigator. The treatments will be given to high-risk patients for up to 24 months to compare their effects on clot prevention. Throughout the study, participants will be closely monitored for any thrombotic or bleeding events. During the trial, researchers will track the time until any arterial or venous blood clots occur, as well as any major or clinically relevant bleeding events. They will also evaluate survival, adherence to therapy, quality of life, and healthcare costs related to these treatments. Participants will have regular follow-ups over 24 months, including assessments for heart rhythm problems and safety monitoring. This comprehensive approach aims to better understand the benefits and risks of DOACs compared to aspirin in preventing clots in MPN patients.