Boulogne Billancourt

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab monotherapy as the first-line treatment for patients with metastatic non-small cell lung cancer mNSCLC whose tumors express high levels of PD-L1. This Phase III, randomized, double-blind, multicenter global study focuses on patients with mNSCLC without certain genetic mutations who are suitable for this treatment approach. Participants are randomly assigned to receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study compares these two drugs over repeated treatment cycles as first-line therapy. Both treatments are biological agents given by infusion, and the study is designed to monitor their effects over up to approximately five years. During the trial, participants will undergo regular assessments including physical exams, imaging scans such as CT or MRI to measure tumor lesions, and laboratory tests to evaluate organ function. Researchers will closely monitor overall survival, progression-free survival, treatment response, duration of response, and patient-reported outcomes on physical functioning and quality of life. Safety and immunogenicity of rilvegostomig will also be evaluated. Participants are followed and assessed for up to five years to gather comprehensive data on treatment effects and long-term outcomes.

Researchers are evaluating the combination of baxdrostat and dapagliflozin in people with chronic kidney disease CKD and high blood pressure hypertension. This Phase III, double-blind, placebo-controlled study aims to assess whether this combination reduces the risk of serious kidney damage, heart failure events, or cardiovascular death compared to dapagliflozin alone. The study includes participants with CKD and hypertension who meet specific kidney function and blood pressure criteria. Participants who are not already taking SGLT2 inhibitors will first complete a 4-week dapagliflozin run-in period. Then, they will be randomly assigned to receive either baxdrostat plus dapagliflozin or a placebo plus dapagliflozin. Baxdrostat dosing may start low and be increased if needed. Study visits will occur at 2, 4, 8, 16, 34, and 52 weeks after randomization, and then approximately every four months until the study ends, which is based on the number of key kidney or heart-related events. Throughout the study, participants will have regular assessments including blood tests to monitor kidney function and potassium levels, blood pressure measurements, and evaluations of heart and kidney health. If participants stop the blinded study drug early, they will continue dapagliflozin if possible and remain in the study for ongoing visits and monitoring. The main outcome is whether the combination treatment reduces the risk of a 50% sustained decline in kidney function, kidney failure, heart failure events, or cardiovascular death over up to 37 months.

Researchers are comparing two treatment combinations for adults with advanced nonsquamous non-small cell lung cancer NSCLC that have a specific KRAS p.G12C mutation and are negative for PD-L1 expression. The study aims to evaluate progression-free survival and overall survival between participants receiving sotorasib with platinum doublet chemotherapy and those receiving pembrolizumab with platinum doublet chemotherapy. This phase 3, randomized, open-label trial is led by Amgen and includes participants with stage IV or advanced stage IIIBC NSCLC. Participants will be randomly assigned to receive either sotorasib orally combined with carboplatin and pemetrexed, or pembrolizumab intravenously combined with the same chemotherapy drugs. These treatments are given as front-line therapy. The study includes a treatment period with these drug combinations and monitoring for outcomes such as response rates and quality of life over several years. During the study, participants will be regularly assessed through various measures including survival status, tumor response, and quality-of-life questionnaires focusing on lung cancer symptoms. Researchers will monitor safety by tracking adverse events, vital signs, and laboratory tests. Treatment concentrations of sotorasib will also be measured up to 64 days after starting. The total study duration includes follow-up for up to approximately 5.5 years to fully evaluate treatment effects and outcomes.

Researchers are evaluating the combination of adagrasib, pembrolizumab, and platinum-doublet chemotherapy compared to placebo plus pembrolizumab and platinum-doublet chemotherapy in adults with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC carrying the KRAS G12C mutation. This Phase 3 trial aims to assess the efficacy, safety, and tolerability of these treatment combinations in this specific patient group. Participants will receive either adagrasib plus pembrolizumab combined with platinum-doublet chemotherapy or placebo plus pembrolizumab and platinum-doublet chemotherapy. Treatments involve specified doses administered on scheduled days, with the chemotherapy consisting of carboplatin or cisplatin along with pemetrexed. Participants are randomly assigned to one of the two study groups and treatments are blinded to ensure unbiased assessment. Throughout the study, participants will undergo regular evaluations including imaging scans to measure tumor response and progression-free survival, as well as assessments of overall survival. Safety is closely monitored by recording adverse events for up to 90 days after the last dose. Quality of life and symptom assessments are also conducted using validated questionnaires. The study duration includes follow-up for up to seven years to gather comprehensive data on treatment outcomes and participant health.

Researchers are evaluating the effectiveness and safety of combining calderasib with pembrolizumab as the first treatment for people with locally advanced or metastatic non-small cell lung cancer NSCLC that has a specific KRAS G12C mutation and a PD-L1 tumor proportion score of 50% or higher. The study compares this combination to pembrolizumab with a placebo to see if it improves the time participants live without the cancer worsening and overall survival. Participants receive pembrolizumab through an intravenous infusion every 21 days for up to 35 cycles. They also take calderasib or a matching placebo by mouth daily until they meet criteria to stop treatment. The study is randomized and double-blind, meaning neither participants nor researchers know who receives calderasib or placebo. During the study, participants will have regular assessments to monitor cancer progression, overall survival, response rate, and quality of life measures through questionnaires. Safety will be closely monitored by tracking adverse events and treatment discontinuations. The study may last up to about 56 months, including follow-up to observe long-term outcomes and quality of life changes.

Researchers are evaluating Risvutatug Rezetecan Ris-Rez, a new medicine targeting specific proteins on cancer cells, in adults with relapsed extensive-stage small cell lung cancer ES-SCLC. This phase 3 study aims to compare how well Ris-Rez works versus the standard treatment, topotecan, by measuring cancer shrinkage, disappearance, and overall survival. The study also monitors safety, side effects, and tolerability of both treatments. Participants will be randomly assigned to receive either Ris-Rez or topotecan. Both treatments will be administered as part of the study to assess their effects. The study will follow participants for up to approximately 139 weeks to evaluate multiple outcomes including survival, tumor response, disease progression, and brain metastasis control. During the study, participants will have regular evaluations including scans, laboratory tests, vital signs, electrocardiograms, and performance status assessments. Researchers will track adverse events, laboratory changes, and participant experiences with the study drugs. The main outcome measured is overall survival up to about 113 weeks, with additional long-term monitoring of other health and disease measures throughout the study.

Researchers are evaluating zipalertinib, an oral drug, for safety, effectiveness, and how it behaves in the body pharmacokinetics in adults with locally advanced or metastatic non-small cell lung cancer NSCLC that has specific mutations in the epidermal growth factor receptor EGFR, including exon 20 insertions and other uncommon mutations. This Phase 2b trial also studies how zipalertinib interacts with other drugs affecting liver enzymes and transporters and aims to find the best dose for treatment. Participants join one of four main groups based on their treatment history and mutation type those previously treated for exon 20 insertion mutations, those who are untreated but not candidates for standard chemotherapy, those with active brain metastases or leptomeningeal disease, and those with other uncommon EGFR mutations without prior systemic therapy. Two additional substudies focus on drug interactions using enzyme and transporter probe cocktails, and dose optimization with participants randomly assigned to two dosing arms. Zipalertinib is taken orally twice daily continuously until disease progression or other reasons to stop. During the study, participants undergo regular evaluations including scans to measure tumor response, brain imaging if applicable, laboratory tests, heart function monitoring, and assessments of side effects. Researchers track how long participants respond to treatment, disease control, survival, and changes in heart electrical activity. Safety and drug concentration in blood are closely monitored. Participants may remain in the study for up to approximately two years to assess these outcomes.

Researchers are evaluating two non-invasive brain stimulation techniques, high frequency repetitive transcranial magnetic stimulation rTMS and accelerated intermittent theta burst stimulation aiTBS, to reduce chronic neuropathic pain lasting at least 6 months. This randomized controlled trial with a crossover design compares these methods to sham stimulation, aiming to assess their analgesic effects and identify factors predicting treatment response. The study includes adults aged 18 to 80 with neuropathic pain and uses brain stimulation targeting pain-related brain regions. The trial involves two treatment phases where participants receive either active or sham stimulation. Active rTMS consists of 5 daily sessions over 5 consecutive days, each lasting 25 to 30 minutes with 1500 pulses per session. Active aiTBS delivers 5 sessions in a single day with breaks between sessions, each lasting about 8 minutes and also delivering 1500 pulses per session. Sham stimulation mimics the active treatments but uses an inactive coil face and low-intensity electrical stimulation to maintain blinding. A 4 to 6-week washout period separates the two treatment phases. Participants undergo about 11 to 12 in-person visits over 10 to 12 weeks. Assessments include self-reported pain diaries using the numeric pain rating scale, validated questionnaires on pain and quality of life, resting-state EEG, and transcranial magnetic stimulation measures of brain excitability. Researchers monitor changes in pain intensity and other outcomes from before treatment through three weeks after treatment. The study also explores neurophysiological and clinical predictors to personalize chronic pain treatment.

Researchers are evaluating the analgesic effects of repetitive Transcranial Magnetic Stimulation rTMS targeting both the motor and prefrontal cortices in adults with fibromyalgia, particularly those with depressive symptoms. This trial aims to improve pain relief by combining stimulation sites, as motor cortex rTMS alone shows inconsistent results in about 40% of patients. Another goal is to develop reliable indicators of rTMS effectiveness using clinical features and brain activity measured by EEG. Participants will receive 10 rTMS sessions over about 2 months, starting with 5 daily sessions in the first week, followed by weekly sessions for 3 weeks, then two sessions spaced two weeks apart. Each session includes high-frequency stimulation to the motor and prefrontal cortices using a specialized coil, with treatment intensity adjusted based on individual motor thresholds. A sham group will receive identical session schedules with a placebo coil and synchronized electrical stimulation to mimic sensations. During the study, participants undergo brain MRI for coil positioning and complete questionnaires assessing pain, fatigue, sleep, mood, and quality of life at baseline, after the intensive treatment week, and two weeks post-treatment. Neurophysiological measures such as EEG and electromyography will also be recorded. The main outcome is change in average pain intensity over 10 weeks, with monitoring of secondary symptoms and safety throughout. Total participation lasts about 10 weeks from enrollment.

This research focuses on adults hospitalized in the ICU with hospital-acquired sepsis caused by multidrug-resistant Gram-negative bacteria. It aims to compare different methods of giving beta-lactam antibiotics and the use of combination versus single antibiotic therapy. The study uses a 2x2 factorial design to evaluate these approaches for their impact on patient outcomes. Participants are randomly assigned to one of four groups that combine two antibiotic infusion strategies and two aminoglycoside dosing durations. The groups include continuous infusion of beta-lactam antibiotics with either a 5-day aminoglycoside infusion or a single dose, and intermittent beta-lactam infusion with the same aminoglycoside options. Treatment is administered according to the assigned group during the ICU stay. Throughout the study, researchers monitor patients for 30 days to assess mortality rates and kidney-related adverse events. Participants undergo bacteriological sampling before treatment and are followed with several clinical and microbiological evaluations, including infection status and organ function. The study tracks outcomes such as survival, kidney events, infection resolution, and length of ICU and hospital stay, with follow-up extending up to 180 days after inclusion.