Grenoble

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

This research investigates how 3D image-guided robot-assisted partial nephrectomy (3D IG-RAPN) compares to the standard conventional robot-assisted partial nephrectomy (RAPN) for patients with moderate to highly complex kidney tumors. The study focuses on peri-operative complications, cancer safety, and long-term kidney function. It aims to determine if treatment with 3D IG-RAPN can improve outcomes during and after surgery. The trial involves two groups: one undergoing 3D IG-RAPN using advanced 3D modeling and augmented reality tools including Synapse 3D and DaVinci Tile-Pro display, and the other receiving conventional RAPN without 3D navigation. This randomized controlled trial enrolls 694 patients at 12 urology centers in France. Patients will be randomly assigned to either the experimental or control group on the day of inclusion. Participants will be monitored for surgical complications, cancer control, and kidney function over time using a composite TRIFECTA score at one month after surgery. Secondary measures include long-term survival, surgeon ergonomics, and satisfaction. Safety and economic evaluations are also planned. Patients must be followed closely with assessments to capture these outcomes throughout the study.

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 evaluating a new classification system for obstructive sleep apnea (OSA) in adults who have recently been diagnosed with this condition. The study aims to monitor long-term improvements both objectively and subjectively in patients with OSA. It focuses on patients who have a diagnosis confirmed by sleep studies and tracks changes in symptoms and cardiovascular measures over time. The study does not involve experimental treatments but observes participants over a period of up to 36 months. During this time, the classification system is applied, and patients are followed to assess changes related to sleepiness and blood pressure. The study is prospective and observational, meaning it follows patients forward in time without assigning specific treatments. Participants will be assessed at enrollment and monitored throughout the observation period. Key measurements include changes in daytime sleepiness using the Epworth Sleepiness Scale and changes in office systolic blood pressure. The study collects data to understand how the new classification relates to patient outcomes over three years, ensuring safety and adherence through regular follow-up visits and evaluations.

Food Protein Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy that mainly appears in infancy and can cause severe vomiting, diarrhea, and dehydration. This condition is often unfamiliar to many clinicians, and its diagnosis relies on specific clinical criteria established in 2017. This study aims to collect detailed clinical information and allergy test results for children diagnosed with acute FPIES and to describe its progression and atypical forms over three years in a French population. The study will include children aged 0 to 17 years with confirmed acute FPIES, diagnosed either by the 2017 JACI clinical criteria or by oral food challenge. Allergy tests such as oral food challenges, skin prick tests, and IgE blood tests will be used to monitor patients. Participants will be seen by allergologists at the start and annually for three years. If tolerance to the offending food is not acquired, an oral food challenge will be conducted in a hospital setting to evaluate resolution. This multicenter French prospective study will gather data on FPIES evolution, including the development of IgE sensitization and clinical symptoms of IgE-mediated allergy. Throughout the study, children will undergo clinical evaluations and allergy testing at inclusion and yearly follow-up visits. Researchers will assess tolerance acquisition over an average of six years, monitor multiple FPIES cases, and record personal atopic conditions. The study will last three years for inclusion and three years of follow-up per patient, aiming to improve management of FPIES in France by understanding its unique food triggers and long-term outcomes.

Malignant hypertension is a very severe type of high blood pressure that can be fatal if not treated. It mainly affects younger adults aged 35 to 55 and carries a high risk of serious heart and kidney problems. Despite its severity and increasing cases, research on malignant hypertension is limited, with diagnostic criteria and treatment guidelines that have not changed since 1929. This study aims to create the first prospective, multicenter registry to better understand the disease's epidemiology, care practices, and biological aspects, and to modernize its definition and diagnosis. The study plans to enroll 500 patients diagnosed with malignant hypertension based on classic criteria, including severe high blood pressure above 180/110 mmHg and evidence of organ damage. It will collect detailed data on patient characteristics, affected organs, and treatment approaches used in various centers. This registry will help develop new diagnostic and treatment recommendations based on solid scientific evidence and may lead to future therapeutic trials. Participants will be followed to evaluate their health outcomes over five years, focusing on their cardiovascular and renal prognosis. Researchers will analyze how patient profiles and the number and type of organ damage affect their long-term outlook. The study will document epidemiology, care pathways, organ involvement, and management strategies in detail to improve understanding and care of malignant hypertension.

Researchers are investigating treatments for adults with metastatic breast cancer that is estrogen receptor-positive, HER2-negative, and expresses gastrin releasing peptide receptor (GRPR). This study focuses on patients who have experienced disease progression after endocrine therapy combined with CDK4/6 inhibitors. The trial aims to find the best doses and schedules of [177Lu]Lu-NeoB combined with capecitabine and to evaluate the preliminary anti-tumor activity of this combination in this patient population. Participants will receive [177Lu]Lu-NeoB, a radioligand therapy, along with capecitabine, a chemotherapy drug. The study includes a phase I dose escalation to determine recommended doses, starting with 150mCi of [177Lu]Lu-NeoB every 6 weeks and capecitabine given twice daily for 14 days followed by 7 days off. Depending on safety, different dose levels and schedules will be explored. Phase II will randomize participants to treatment regimens based on phase I results. Imaging with [68Ga]Ga-NeoB PET/CT or PET/MRI will be performed during screening and after treatment in phase II to assess tumor GRPR expression. Participants will attend study visits approximately every 3 weeks for the first 9 months, then every 6 weeks, for treatment administration, safety monitoring, and tumor assessments. Tumor scans occur every 9 weeks until month 18, then every 12 weeks until month 36, and as needed afterwards. After stopping treatment, safety follow-up lasts 8 weeks, with longer-term follow-up for up to 5 years. Researchers will monitor safety, dose tolerability, tumor response, progression-free and overall survival, and other outcomes related to treatment effectiveness and side effects.

Researchers are studying patients with completely removed non-small cell lung cancer (NSCLC) who have common EGFR mutations (L858R and Del19). The study aims to include broad-panel centralized genetic testing at the start to better understand factors predicting outcomes and resistance to the drug osimertinib when used after surgery. It also investigates the molecular changes linked to cancer returning during or after osimertinib treatment to find better treatment options if the cancer comes back in a metastatic form. The study involves collecting plasma circulating tumor DNA (ctDNA) samples before surgery (optional), 4 to 8 weeks after surgery, before starting any adjuvant chemotherapy or osimertinib treatment, every six months during follow-up, and at relapse. Tumor tissue samples from surgery and optionally at relapse are also collected for molecular analysis. Patients may receive adjuvant chemotherapy if needed before starting osimertinib, which is given with the intent to treat for three years. Participants will be regularly followed every 3 to 6 months according to standard recommendations. Researchers will monitor genetic markers using blood and tissue samples to study cancer relapse and resistance. The main outcome is to assess the feasibility of this molecular monitoring approach over an 18-month period. Safety and long-term follow-up are included, aiming to improve treatment decisions for patients with resected NSCLC and EGFR mutations.

Researchers are studying the real-world effectiveness of pegcetacoplan in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). This long-term, multicenter observational study aims to fill knowledge gaps about how pegcetacoplan works in routine medical practice. It also seeks to provide important information on red blood cell transfusions and healthcare resource use before and after starting pegcetacoplan treatment. Patients who have started pegcetacoplan treatment within the last 12 months or are prescribed it at enrollment will be followed for approximately 36 months. The study will collect both retrospective data from up to 12 months before treatment start and prospective data during treatment, with a total data collection period of up to about 48 months. After stopping pegcetacoplan, patients will remain in the study for 8 weeks to monitor for any adverse events. Participants will attend their usual medical visits, and data from these visits will be collected, including effectiveness measures, safety reports, patient- and clinician-reported outcomes, and healthcare use. The primary outcome includes changes in hemoglobin levels over 6 months from the start of pegcetacoplan treatment. The study plans to enroll about 200 patients across multiple countries, and data collection includes both retrospective and prospective periods, capturing comprehensive information on pegcetacoplan use in real-world settings.

Researchers are studying whether baricitinib can help preserve beta-cell function in children and adults newly diagnosed with type 1 diabetes. This Phase 3 trial focuses on participants aged 1 to less than 36 years who have recently been diagnosed with this condition. The goal is to understand if baricitinib, compared to a placebo, can maintain insulin-producing cell activity. Participants will be randomly assigned to receive either baricitinib or a placebo, both given orally. The study is double-blind, meaning neither participants nor researchers know who receives the active drug or placebo. Treatment and observation will continue for about 60 weeks. During the study, participants will undergo evaluations including measuring C-peptide levels to assess beta-cell function at the start and after 52 weeks. Researchers will monitor health status, collect laboratory tests, and track any side effects or changes in diabetes-related markers to determine the effects of baricitinib over the study period.