Biliary Tract Cancer

Researchers are evaluating a new PET imaging tracer called [18F]FAPI-74 to detect cancer by targeting the fibroblast-activation protein (FAP) found in cancer-associated fibroblasts. This study aims to compare [18F]FAPI-74 PET scans to the standard [18F]-FDG PET scans and other imaging methods like CT or MRI across several cancers including pancreatic ductal adenocarcinoma, cholangiocarcinoma, hepatocellular carcinoma, gastric, bladder, ovarian cancers, pheochromocytoma/paraganglioma, small cell lung cancer, neuroendocrine cancer, mesothelioma, and sarcoma. The study is a phase 2 interventional trial conducted by the National Cancer Institute (NCI). Participants will receive an intravenous dose of [18F]FAPI-74 before undergoing PET/CT imaging about one hour later. They will also have a baseline FDG PET scan within one week. If tumors are detected by [18F]FAPI-74, additional scans using this tracer and FDG may be repeated during routine treatment and if cancer progresses within two years. Those with negative baseline [18F]FAPI-74 scans will not have repeated scans but remain in follow-up. The study involves a single arm where participants undergo both types of PET imaging. During the study, participants will have scans at baseline and potentially at subsequent treatment or progression points. Safety monitoring includes observation for reactions to the tracer up to three days after injection. Researchers will measure the mean number of lesions, standardized uptake values at baseline, post-treatment, and recurrence. Follow-up calls will continue for two years to assess progression-free survival and overall survival. The total participation duration includes imaging visits and two years of follow-up monitoring.

Researchers are evaluating the diagnostic value of a new protein-specific probe called 18F-T2 in PET/CT imaging for people with solid tumors that are likely to express high levels of CAIX protein. The study will also assess how safe and tolerable the 18F-T2 injection is, as well as measure its radiation dosage. This research is important to better understand how well 18F-T2 can detect these tumors compared to standard imaging techniques. Participants with tumors suspected to express high levels of CAIX will receive an intravenous injection of 18F-T2. About an hour after the injection, PET/CT imaging will be performed to capture detailed images of the tumors. Within one week, participants will also undergo a whole-body PET/CT scan using 18F-FDG, a commonly used imaging agent, to allow comparison between the two imaging methods. During the study, participants will be monitored for any adverse events within 24 hours after the 18F-T2 injection to evaluate safety and tolerability. Researchers will measure the diagnostic sensitivity and specificity of 18F-T2 PET/CT for detecting CAIX-positive tumors. They will also assess uptake values in tumors on both 18F-T2 and 18F-FDG scans, analyze the correlation between 18F-T2 uptake and CAIX expression in tissue samples, and evaluate radiation dosimetry. The study will continue until one month after completion for outcome assessments.

Researchers are evaluating the clinical use of [68Ga]Ga-FAPI-46 PET/CT imaging in patients with pancreatic or bile duct cancer. This study aims to find the best timing and scan protocol, test the repeatability of the scan results, and assess the accuracy of this imaging method to detect pancreatic cancer and monitor chemotherapy effects. The study is divided into three parts, with each participant joining only one part. In part A, participants will have one [68Ga]Ga-FAPI-46 PET/CT scan and receive two venous cannulas and one arterial cannula. Part B involves two scans with a venous cannula for each. Part C includes two scans with venous cannulas and focuses on patients eligible for neoadjuvant therapy before surgery. The study evaluates the tracer's pharmacokinetics, repeatability, and diagnostic accuracy. Participants will undergo PET/CT scans and have cannulas placed as needed. Researchers will collect blood activity measurements, plasma to blood ratios, and semi-quantitative tracer uptake data. They will assess repeatability, diagnostic accuracy, and therapy response monitoring over three months. Safety and agreement between imaging and pathology will also be evaluated during and after scans.

Biliary tract carcinoma (BTC) includes cancers of the gallbladder, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. It is a highly aggressive cancer with poor outcomes, ranking sixth in gastrointestinal cancer incidence and tenth in cancer-related deaths worldwide. Because early symptoms are often absent and the disease tends to recur and spread, only about 16.5% of patients can have curative surgery, and the overall 5-year survival rate is under 5%. Early and accurate detection is crucial to improve patient outcomes. This research aims to assess the use of cell-free DNA (cfDNA) methylation in blood as a liquid biopsy for diagnosing and managing BTC. The study involves several groups, including healthy individuals, patients with confirmed benign biliary lesions, other gastrointestinal cancers, and those with confirmed or suspected BTC. Researchers will analyze methylation patterns in circulating tumor DNA (ctDNA), a small fraction of cfDNA that carries tumor genetic and epigenetic information. This approach is studied for its potential to detect BTC early, assist in differential diagnosis, monitor prognosis, and guide therapy. Different cohorts serve as internal training, validation sets, and independent validation groups. Participants will provide blood samples and undergo clinical evaluations to measure the accuracy of the ctDNA methylation test in diagnosing BTC. The study will assess diagnostic performance by cancer subtype and stage, and ability to distinguish BTC from other conditions. Vital signs, organ function, and other health markers will be monitored to ensure participant safety. The study welcomes adults aged 18 to 80 years, with follow-up and assessments continuing until May 2026 to evaluate the test's clinical utility.

Researchers are studying sacituzumab tirumotecan, alone or combined with other treatments, to see if it can treat certain advanced or unresectable gastrointestinal cancers, including colorectal cancer, pancreatic ductal adenocarcinoma, and biliary tract cancer. The study aims to learn about the safety and tolerance of sacituzumab tirumotecan and how many participants experience a reduction or disappearance of their cancer. Participants receive sacituzumab tirumotecan at one of two dose levels, either alone or with chemotherapy given every two weeks, or with cisplatin and pembrolizumab on a three-week cycle. Treatments continue until the cancer worsens or side effects prevent further treatment. Rescue medications and supportive care are also provided to help manage side effects. During the study, researchers monitor participants for side effects, treatment tolerance, and cancer response using standard criteria. Outcomes include the number of participants experiencing dose-limiting toxicities, adverse events, discontinuation due to side effects, and objective response rates. The study may last up to approximately 63 months, with ongoing safety and efficacy evaluations throughout.

Researchers are evaluating the safety and effectiveness of a modified herpes simplex virus called recombinant oncolytic herpes simplex virus type 1 (R130) in patients with advanced solid tumors. This early phase 1, open, single-arm clinical trial aims to study the treatment in people with various cancers such as sarcoma, carcinoma, digestive cancer, breast cancer, lung cancer, brain cancer, melanoma, gynecologic cancer, head and neck cancer, and kidney cancer. The study focuses on patients who have not responded to standard treatments or who choose not to receive other antitumor therapies. Participants will receive injections of 1 to 2 milliliters of R130 at a concentration of 1x10^8 plaque-forming units per milliliter into their tumors or abdominal cavity every 7 to 14 days. This approach allows the virus to be delivered directly to the cancer site. The study involves only one treatment group receiving the R130 virus, and no placebo or comparison group is used. During the trial, researchers will monitor participants for adverse events and laboratory abnormalities up to 6 months and assess their immune response. Disease control and response duration will be evaluated every 10 weeks for up to 12 months, while quality of life assessments will occur every 6 weeks for the same period. Participants will undergo regular laboratory tests and clinical evaluations to track safety and treatment impact. The total study duration for each participant may extend up to one year with ongoing monitoring.

Researchers are evaluating the safety, tolerability, and efficacy of intravenous HNF4α srRNA treatment in adults with advanced intrahepatic cholangiocarcinoma (ICC), a type of liver cancer. This early phase 1, single-arm, open-label pilot study aims to assess how well patients tolerate the treatment and its effects on tumor response and survival. The study also explores the impact of the drug on tumor biomarkers and patient-reported outcomes over an average period of two years. Participants will receive HNF4α srRNA intravenously through a peripheral vein. The dosing schedule includes a second dose about 14 days after the initial treatment, followed by subsequent doses approximately every 28 days. Dose adjustments may be made based on patient tolerance and response. This dose escalation study tests increasing doses of 25, 50, and 100 micrograms. After at least four treatment cycles, some patients with stable or progressive disease may continue treatment combined with immunotherapy, targeted therapy, or chemotherapy, with doses adjusted as needed. During the study, participants will be closely monitored for safety and tolerability during a 14-day observation after the first dose. Researchers will regularly assess tumor response using RECIST v1.1 criteria and collect data on progression-free survival, overall survival, and quality of life through patient-reported outcomes. Laboratory tests, tumor biomarker analysis, and clinical evaluations will occur throughout the treatment and follow-up period lasting up to two years. The study aims to provide detailed information on treatment effects and participant experiences over time.

Researchers are studying the use of C-13-60 cells, a type of chimeric antigen receptor T cell therapy (CAR-T), for treating patients with advanced malignant solid tumors that test positive for carcinoembryonic antigen (CEA). This phase I, single-arm, open-label trial aims to assess the safety, tolerability, and how the drug behaves in the body, while also making early observations on its effectiveness. The study focuses on finding the appropriate dose for future phase II trials in various cancers including colorectal, esophageal, gastric, pancreatic, non-small cell lung, breast, and bile duct cancers. Participants will receive intravenous infusions of CEA-targeted CAR-T cells, with doses increasing stepwise from 2 to 10 million cells per kilogram of body weight. Before the cell infusion, patients undergo conditioning chemotherapy with Fludarabine and Cyclophosphamide to prepare the body. The dose escalation follows strict safety rules: groups of patients receive increasing doses, and if severe toxicity occurs, the treatment is adjusted or stopped based on safety committee decisions. The trial includes a 28-day period of monitoring for dose-limiting toxicities after each infusion. Throughout the study, participants will have regular evaluations including tumor assessments, laboratory tests, and monitoring of cell levels in the blood. Researchers will track safety outcomes such as dose-limiting toxicities and maximum tolerated dose within one month. They will also measure disease control rates and various pharmacokinetic indicators over three months. The trial requires participants to agree to contraception use and undergo follow-up to evaluate treatment impact and safety. The overall study duration extends until the end of 2027, with detailed monitoring during and after treatment.

This research aims to describe the clinical, histological, and radiological features of rare primary liver cancers. It focuses on collecting tumor and blood samples to better understand these cancers and to evaluate how well treatments used in real-world practice work, with the goal of identifying the best treatment sequences. The study serves as a foundation for future research to find new molecular and imaging biomarkers that could improve diagnosis and prognosis. The study is observational and retrospective, meaning it reviews past cases from multiple centers in France. It collects biological samples and clinical data from patients diagnosed with rare primary liver cancers after January 2018. The study evaluates treatments patients have received in clinical practice without assigning any new treatments or interventions. Participants' data, including clinical characteristics, tumor biology, and imaging, will be reviewed for up to five years from diagnosis. Researchers will measure outcomes such as recurrence-free survival for patients without metastases, progression-free survival for those with metastases, and overall survival. The study includes both living patients who consent to participate and deceased patients, aiming to gather comprehensive information to support future translational studies.

Gastrointestinal (GI) cancers, including hepatocellular carcinoma, cholangiocarcinoma, pancreatic ductal adenocarcinoma, esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer, continue to be a significant global health concern. This research aims to develop a noninvasive screening test using circulating microRNAs (miRNAs) to better detect these cancers early. Current methods like endoscopy and imaging are invasive or less sensitive, making early diagnosis difficult and limiting treatment options. The study seeks to create a cost-effective and practical miRNA signature to improve early detection and outcomes for patients. This study uses a retrospective international cohort of blood samples from patients with various GI cancers and non-cancer controls, including healthy volunteers and those with benign conditions. Small RNA sequencing will identify miRNA profiles, and advanced machine learning methods will be applied to develop a miRNA panel that can distinguish cancer from non-cancer cases and differentiate among cancer types. The study includes discovery, modeling, and validation phases across multiple centers and diverse populations to ensure the panel's accuracy and reliability. Participants contribute by providing blood samples collected before treatment, and researchers will analyze these samples along with clinical and demographic data. The study will assess the diagnostic accuracy of the miRNA panel at baseline, focusing on its ability to detect early-stage cancers and distinguish cancer subtypes. This observational study involves no treatment interventions, and participation mainly consists of data and sample analysis. The study is expected to continue until June 2026, with ongoing monitoring of the miRNA panel's performance.