Castellana Grotte

Researchers are studying the safety and effectiveness of long-acting antibodies given alone or in combinations to adults with moderately to severely active ulcerative colitis (UC). This Phase 2, multicenter platform trial aims to find treatments that can improve symptoms and induce remission in people diagnosed with UC for at least 3 months. The study includes participants with active disease confirmed by endoscopy and histology and with moderate to severe symptoms based on a scoring system. The trial has two parts. Part A is an open-label phase testing three different monotherapy drugs to assess safety and initial effectiveness. Part B will be a randomized, placebo-controlled phase where participants receive one of six interventions (three monotherapies or three combinations) or placebo to compare outcomes. Treatments involve intravenous (IV) induction followed by subcutaneous (SC) maintenance dosing. Different treatment arms may start and finish at varying times during the study. Participants will undergo endoscopy and histology to confirm disease activity at screening, with regular monitoring throughout the study. Researchers will evaluate changes in disease severity using the Robarts Histopathology Index and measure the percentage of participants achieving clinical remission by Week 12. Safety and efficacy will be closely followed during and after treatment. The total study duration depends on treatment arm timelines and follow-up requirements.

Researchers are investigating the effectiveness and safety of rilvegostomig combined with gemcitabine plus cisplatin compared to durvalumab combined with gemcitabine plus cisplatin as first-line treatments for patients with advanced biliary tract cancer, including cholangiocarcinoma and gallbladder carcinoma. This is a global, phase III, randomized, open-label study focused on patients with unresectable locally advanced or metastatic disease who have not previously received treatment for advanced cancer. The study includes patients with known PD-L1 status and measurable tumors suitable for repeated evaluation. Participants will receive either rilvegostomig intravenously every three weeks along with gemcitabine and cisplatin given intravenously on days 1 and 8 of each 21-day cycle, or durvalumab intravenously every three weeks for up to eight cycles, followed by dosing every four weeks, along with the same chemotherapy regimen. Treatment is designed to evaluate first-line therapy effects, comparing these two immunotherapy combinations alongside standard chemotherapy. Throughout the study, patients will be closely monitored for overall survival, especially in those with PD-L1 expression of 1% or higher, over approximately four years. Assessments will include tumor measurements by CT or MRI using RECIST 1.1 criteria, performance status evaluations, and ongoing safety monitoring. The study aims to understand the impact of these treatments on survival and disease progression in advanced biliary tract cancer patients.

This research aims to evaluate the effectiveness of trastuzumab deruxtecan (T-DXd) in adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously been treated with a trastuzumab-based regimen. The study also collects patient demographic and clinical information, treatment patterns, and safety data including serious adverse events and drug reactions. It includes a disease registry for patients receiving conventional therapies in a real-world European setting. The study is non-interventional, meaning no investigational drugs are administered beyond standard care. Patients receiving T-DXd will be treated according to the Summary of Product Characteristics (SmPC), and data on conventional therapies such as platinum-fluoropyrimidine chemotherapy, nivolumab, ramucirumab-paclitaxel, taxane, irinotecan, and pembrolizumab will also be gathered. Treatment choices and administration follow the physician's decision and routine clinical practice. Participants will be monitored from baseline to about two years to assess the time to next treatment. Researchers will collect clinical data, treatment details, tolerability, and patient surveys to understand outcomes and safety. The study involves regular follow-up and data collection to track treatment effectiveness and patient experience in real-world settings.

Crohn's disease is a chronic inflammatory condition of the digestive tract that cannot be cured. This research aims to evaluate how effective two approved drugs, upadacitinib and risankizumab, are as second-line treatments for adults with moderate-to-severe Crohn's Disease in real-world clinical settings. The study includes patients who have previously used a first-line treatment and now need additional therapy. Participants will be prescribed either upadacitinib or risankizumab by their doctors following routine medical practice and local guidelines. The study has a retrospective phase looking back up to 2 years before enrollment and a prospective phase lasting up to 18 months after enrollment. There are no additional procedures or burdens expected for participants beyond their usual care. During the study, researchers will track how many participants achieve remission without corticosteroids after 12 months. Participants' medical records will be reviewed, and their health monitored over time according to standard care. The total follow-up will allow assessment of the long-term effectiveness and safety of these treatments in routine practice.

This research aims to evaluate the safety and effectiveness of pumitamig combined with chemotherapy compared to bevacizumab combined with chemotherapy in adults with previously untreated, unresectable, or metastatic colorectal cancer. The study is a blinded, randomized Phase 2/3 trial targeting participants with histologically confirmed recurrent or metastatic colorectal adenocarcinoma that cannot be cured with surgery. Participants must not have certain genetic markers such as mismatch repair deficiency, microsatellite instability-high status, or BRAF V600E mutation. Participants will receive either pumitamig or bevacizumab along with chemotherapy regimens including FOLFOX, FOLFIRI, or CAPOX at specified doses and schedules. The interventions involve administering these drugs on specified days, though exact dosing details are not provided. The study compares these two treatment combinations to assess their safety and efficacy in this patient population. Throughout the study, participants will be monitored for tumor response using RECIST v1.1 criteria, progression-free survival, and overall survival for up to five years. Researchers will evaluate confirmed complete or partial tumor responses, survival rates, and disease progression. The study includes regular assessments to track treatment effects and safety over a long-term follow-up period, ensuring comprehensive monitoring of participant outcomes.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer-related death. Most cases develop in a cirrhotic liver, where scarring makes treatment more difficult. This research aims to collect and analyze data from patients treated in everyday medical settings to understand how new combinations of immunotherapy drugs, like atezolizumab-bevacizumab and durvalumab-tremelimumab, work in real life. The study also seeks to find the best order of treatments and clinical markers that predict how well patients respond to these therapies. The study observes patients receiving frontline systemic treatments, including atezolizumab-bevacizumab or other immunotherapy combinations. It focuses on patients with advanced liver cancer who are not candidates for local treatments like surgery. While no specific interventions are assigned by the study, it collects data on treatment sequences and responses to these immunotherapies over time. Participants will be monitored from enrollment for up to three years to evaluate treatment safety and toxicity as first-line therapy. Researchers will gather clinical and laboratory data to identify markers predicting treatment outcomes and examine how factors like disease progression and second-line therapies impact survival. This long-term follow-up aims to provide real-world evidence to guide future treatment decisions for liver cancer patients.

This research focuses on patients with obesity (BMI >30 kg/m2) who also have liver-related diseases such as hepatic steatosis or other hepato-biliary pathologies. Obesity is a chronic condition linked to several health problems including hypertension and diabetes, which impact survival and quality of life. The study aims to investigate changes in lipid profiles, immune factors, and circulating microRNAs in these patients, especially in relation to different treatment approaches including dietary programs and bariatric surgery. Participants in this study will follow one of two main treatment paths: a nutritional approach involving diet and multidisciplinary support including psychological care, or bariatric surgery, which may include techniques like intragastric balloons, gastric bypass, or sleeve gastrectomy. The choice of treatment is guided by a multidisciplinary team and depends on the patient’s health status and suitability for surgery. Those unsuitable for surgery will continue with dietary interventions supervised by a team including doctors, dietitians, psychologists, and kinesiologists. During the study, researchers will assess changes in lipidomic parameters, blood chemistry related to liver disease and fibrosis, and microRNA profiles at the start and after one year. Patients will undergo evaluations including ultrasound and Fibroscan for liver assessment. The study monitors metabolic and inflammatory changes linked to obesity and treatments, aiming to understand how weight loss and therapies affect cellular and immune functions over time.

Researchers are evaluating the effects of continuing cetuximab treatment beyond first-line progression in adults with metastatic colorectal cancer whose tumors have specific genetic characteristics, including RAS and BRAF wild-type status. This Phase 3 trial aims to compare chemotherapy combined with cetuximab against chemotherapy combined with bevacizumab to see if cetuximab continuation improves tumor response, progression-free survival, overall survival, and safety. The study builds on earlier trials suggesting potential benefits of cetuximab continuation in this patient group. Participants will receive a standard chemotherapy regimen, either FOLFOX or FOLFIRI, combined with either cetuximab or bevacizumab every two weeks. Cetuximab is administered as an intravenous infusion of 500 mg/m² every 14 days, while bevacizumab is given at 5 mg/kg every 14 days. Treatment continues until disease progression, unacceptable side effects, or withdrawal of consent. Tumor response will be regularly assessed using imaging scans according to RECIST criteria. Throughout the study, patients will undergo regular CT or MRI scans, laboratory tests, and clinical evaluations to monitor disease status and safety. Biological samples such as tumor tissue, blood, and stool will be collected for research on treatment resistance and the gut microbiome. The primary outcome is the overall response rate measured from randomization until progression, death, or study completion, with assessments continuing up to 48 months. Approximately 360 patients will participate across sites in Italy and Spain.

Researchers are evaluating how two different exercise programs combined with a Low Glycaemic Index Mediterranean Diet (LGIMD) compare to diet alone in affecting inflammation in adults aged 18 to 65 years who have obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). The study aims to measure changes in systemic inflammation and related biomarkers after a four-month intervention. Secondary goals include assessing changes in body composition, physical fitness, gut microbiota, quality of life, and fatty acid profiles in these patients. Participants will be randomly assigned to one of three groups: one group will follow the LGIMD while performing moderate-intensity aerobic exercise (outdoor walking) four times a week for 60 minutes each session; another group will follow the same diet combined with high-intensity interval training (HIIT) three times a week for 50 minutes per session in a gym; and a third group will follow only the LGIMD without added exercise. All interventions last for four months and are supervised by specialized staff. During the study, researchers will monitor participants' inflammation levels at the start and after 120 days, along with measuring physical fitness, body composition, gut microbiota composition, and quality of life through questionnaires. Regular assessments will include biomarker testing for inflammatory markers such as TNF-alpha, IL-1, IL-6, IL-10, CK-18, PCR, and VES. The study will also evaluate the fatty acid profile of red blood cell membranes. Participants' adherence to diet and exercise will be supported and tracked by the study team throughout the four-month period.

Researchers are studying adults with obesity, defined as a body mass index (BMI) over 30 or a large waist circumference, to understand how obesity affects gut permeability and liver steatosis. The study aims to see if a very low calorie ketogenic diet (VLCKD) can improve these conditions over six weeks. This research focuses on the ability of the intestinal barrier to block harmful substances and on the buildup of fat in the liver, known as non-alcoholic fatty liver disease (NAFLD). All participants will follow a very low calorie ketogenic diet for six weeks. This diet is designed to be low in calories and high in fats, promoting a state called ketosis. The study has only one group, so everyone receives the same dietary intervention to evaluate its effects on gut health and liver fat. During the study, participants will be monitored for changes in gut permeability and liver steatosis using specific diagnostic tools and markers. The main outcomes measured are gut permeability and signs of gut imbalance (dysbiosis) after six weeks. The total study duration for each participant corresponds to this six-week dietary treatment period.