Castellana Grotte

Researchers are evaluating the use of epigenome-guided treatment selection compared to the usual standard-of-care SOC treatment for adults with active Crohns Disease CD. This study aims to assess the effectiveness, safety, and cost-effectiveness of using an epigenetic biomarker assay and machine-learning software called EpiPredict to help choose between two biologic therapies, Vedolizumab VDZ and Ustekinumab UST, for treating active CD. The trial includes participants who have active disease and are either new to biologic therapy or have had limited prior biologic exposure. Participants will be randomly assigned to one of two groups one group will receive biologic treatment guided by the EpiPredict software based on epigenetic blood tests, which indicates the likelihood of response to VDZ or UST, while the other group will receive biologic therapy following usual SOC without epigenetic guidance. Both groups will receive their biologic therapy according to approved product labels, with dose adjustments allowed as needed by the treating doctor. Treatment and assessments will be carried out over 26 weeks, with different assessment schedules depending on the biologic received. After this treatment period, participants will have long-term follow-up every six months up to 24 months. During the study, participants will provide blood samples for epigenetic testing and undergo clinical and endoscopic evaluations to monitor their disease activity and response to treatment. Data will also be collected from routine medical records and online questionnaires during follow-up visits. The primary measurement is the comparison of clinical remission and endoscopic response rates at Week 26 between the two treatment selection methods. Researchers will also evaluate cost-effectiveness and explore how well the epigenetic assay predicts treatment success. Participants are required to comply with study procedures and provide informed consent to participate fully.

Researchers are evaluating the safety and effectiveness of several long-acting antibody treatments for adults with moderately to severely active ulcerative colitis UC. This Phase 2, multicenter platform study aims to compare multiple investigational therapies, including both single agents and combinations, to better understand their potential benefits and risks. The study is sponsored by Spyre Therapeutics, Inc. and involves adults aged 18 to 75 years with active UC confirmed by endoscopy and histology.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with gemcitabine plus cisplatin compared to durvalumab combined with gemcitabine plus cisplatin as a first-line treatment for patients with advanced biliary tract cancer BTC. This phase III, randomized, open-label study aims to improve treatment options for patients with unresectable locally advanced or metastatic BTC who have not received prior therapy for advanced disease. The study focuses on overall survival and other important outcomes over approximately four years. Participants receive either rilvegostomig or durvalumab through intravenous infusion along with chemotherapy drugs gemcitabine and cisplatin. Durvalumab is given every three weeks for up to eight cycles, then every four weeks. Gemcitabine and cisplatin are administered intravenously on Days 1 and 8 of each 21-day cycle. The study compares these two treatment combinations to assess their effects on survival, disease progression, tumor response, and safety. During the study, participants undergo regular assessments including imaging scans like CT or MRI to measure disease status, laboratory tests to evaluate organ function, and evaluations of symptoms and quality of life. Researchers monitor drug levels and immune response markers. The study lasts about four years, with ongoing safety and health status monitoring throughout. Patient-reported symptoms and quality of life are assessed up to 12 weeks after disease progression.

Researchers are evaluating trastuzumab deruxtecan T-DXd as a treatment for adult patients with advanced HER2-positive gastric or gastroesophageal junction GEJ adenocarcinoma who have previously received a trastuzumab-based regimen. This study aims to assess the real-world effectiveness of T-DXd, patient characteristics, treatment patterns, and safety in this population. It also includes data collection on patients receiving conventional therapies for exploratory comparison. This is a non-interventional observational study where patients receive T-DXd or conventional therapies as part of routine clinical care according to approved guidelines SmPC. No investigational drugs are given. The study tracks patients starting T-DXd as a second-line or later treatment and collects data on other therapies such as chemotherapy and immunotherapy used in clinical practice. Participants will be followed for up to approximately 2 years from baseline to monitor outcomes including time to next treatment, changes in treatment, physician-reported safety events, use of prophylactic treatments, and quality of life using validated questionnaires. Data on physician visits, treatment discontinuation, and safety events will also be collected to understand treatment tolerability and patient experience in a real-world setting.

This research focuses on adults with moderate-to-severe Crohns Disease CD, a chronic inflammatory condition of the digestive tract. It aims to evaluate how effective two approved drugs, upadacitinib and risankizumab, are as second-line treatments for CD in real-world clinical settings. Approximately 250 participants prescribed either drug by their physicians will be enrolled across 25 sites in Italy. Participants will receive either upadacitinib or risankizumab as part of their usual medical care, following local prescribing guidelines. The study includes a retrospective phase looking back up to 2 years before enrollment and a prospective phase where participants will be observed for up to 18 months after starting the medication. Both groups will be followed from their first dose throughout the study period. During this time, participants will not experience any additional study-related burden beyond their routine care. Researchers will review clinical records and monitor outcomes such as the percentage of participants achieving corticosteroid-free remission at 12 months. The study aims to gather real-world data on these treatments effectiveness and safety over time, with no extra visits or procedures required beyond standard practice.

This trial studies participants with previously untreated, unresectable, or metastatic colorectal cancer. It evaluates the safety and effectiveness of pumitamig combined with chemotherapy compared to bevacizumab combined with chemotherapy. The study includes participants who do not have specific genetic markers like dMMR, MSI-H, or BRAF V600E mutations, which may affect treatment response. Participants receive treatment with study drugs such as pumitamig, bevacizumab, and chemotherapy regimens including FOLFOX, FOLFIRI, and CAPOX. The treatments are given at specified doses on specific days. The study uses a randomized, double-blind design with multiple experimental and comparator arms to assess these combinations. Throughout the study, participants undergo regular assessments to measure tumor response and survival outcomes. Key evaluations include imaging tests using RECIST v1.1 criteria, monitored by both investigators and independent reviewers, over a period of up to 5 years. Researchers track objective response, progression-free survival, and overall survival to determine treatment outcomes and safety.

Hepatocellular carcinoma HCC is a common and deadly form of liver cancer that often develops in a liver damaged by scarring, making treatment difficult. This research is collecting and analyzing real-world patient data to evaluate the safety and effectiveness of new immunotherapy combinations like atezolizumab-bevacizumab and durvalumab-tremelimumab, and to find the best treatment sequences for advanced liver cancer. The study also aims to identify clinical and laboratory markers that predict how patients respond to these treatments to help personalize care. Participants in this observational study are patients with advanced liver cancer who are receiving frontline systemic therapy with atezolizumab-bevacizumab or other immunotherapies. The study collects data from everyday clinical practice without altering treatments. It focuses on new treatment combinations approved in recent years and aims to understand their real-world use and outcomes. The study monitors patients for up to three years from the start of their therapy. During the study, researchers review patient health, treatment responses, and side effects, tracking outcomes like toxicity, progression-free survival, overall survival, response rates, and eligibility for second-line treatments. Safety is monitored throughout the three-year period to provide comprehensive information on how these therapies work outside of clinical trials. This data will help guide future treatment decisions for liver cancer patients.

Researchers are investigating changes in the lipidomic, immunological, and circulating microRNA profiles in adults with obesity and hepato-biliary diseases, such as hepatic steatosis or gallbladder inflammation. The study compares patients undergoing a dietary program with those receiving bariatric surgery, aiming to understand how these treatments affect metabolic and inflammatory changes related to obesity and liver pathology. This observational study considers the complex nature of obesity and its impact on patient health and quality of life. Participants will either follow a nutritional approach guided by a multidisciplinary team including doctors, dieticians, psychologists, and kinesiologists, or undergo bariatric surgery such as intragastric balloons, gastric bypass RYGB, or sleeve gastrectomy. The choice of intervention depends on the surgeons recommendation and the patients health status. Patients not suitable for surgery will be managed with dietary programs, emphasizing psychological support to address eating behavior disorders. During the study, researchers will assess lipidomic parameters, routine blood chemistry related to liver disease and fibrosis, and microRNA profiles at the start and after one year. Participants will be monitored through clinical visits, imaging like ultrasound and Fibroscan, and laboratory tests. The goal is to evaluate metabolic and inflammatory changes over time with each intervention, helping to inform future treatment strategies for obesity and associated liver conditions.

Researchers are evaluating whether continuing cetuximab treatment beyond first-line progression can improve outcomes in adults with metastatic colorectal cancer who have tumors that are RAS and BRAF wild-type. This Phase 3 clinical trial aims to compare chemotherapy combined with cetuximab versus chemotherapy combined with bevacizumab, focusing on tumor response, progression-free survival, overall survival, and safety. The study builds on prior trials suggesting potential benefits of cetuximab continuation in this patient group. Participants will be randomly assigned to receive either FOLFOX or FOLFIRI chemotherapy combined with cetuximab experimental group or bevacizumab control group. Treatments are given every two weeks, with cetuximab administered as a 120-minute intravenous infusion at 500 mgm and bevacizumab at 5 mgkg. Therapy continues until disease progression, unacceptable side effects, or patient withdrawal. Tumor response will be assessed by independent review using RECIST criteria. During the study, patients undergo regular CT or MRI scans, laboratory tests, and clinical evaluations. Biological samples such as tumor tissue, blood, and stool are collected for research on resistance mechanisms and the gut microbiome. The primary measure is the overall response rate assessed up to 48 months, with secondary outcomes including overall survival, progression-free survival, and safety monitored throughout treatment and up to 30 days after the last dose. Participation lasts through treatment and follow-up periods up to several years.

Researchers are investigating how two different exercise programs combined with a Mediterranean diet compare to the diet alone in reducing inflammation among adults aged 18 to 65 years who have obesity and Non-Alcoholic Fatty Liver Disease NAFLD. The study aims to measure various inflammatory markers and understand the impact on body composition, physical fitness, gut microbiota, quality of life, and fatty acid profiles after a 4-month intervention. Participants will be randomly assigned to one of three groups one group will follow the Mediterranean diet and engage in moderate-intensity aerobic exercise outdoor walking for 180 minutes per week another will follow the diet combined with high-intensity interval training HIIT in a gym setting for 150 minutes per week and the third group will follow the Mediterranean diet alone. All participants will receive guidance from specialized staff on both diet and exercise. During the study, participants will undergo assessments at the start, midpoint, and end of the 4 months, including measurements of systemic inflammation, body composition, gut microbiota analysis, quality of life questionnaires, fatty acid profiles, and evaluations related to sarcopenia risk and intestinal health. The primary outcome focuses on changes in systemic inflammatory status between baseline and day 120. The study will include monitoring to ensure adherence and safety throughout the participation period.