Hepatocellular Carcinoma (HCC)

Researchers are studying chronic liver diseases and tumors, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). These conditions can be caused by viral infections like hepatitis B, C, and D or lifestyle factors such as overeating and lack of exercise. The goal is to develop better understanding and new treatments by analyzing liver tissues and tumors at the single-cell level to identify therapeutic targets and improve patient outcomes. The study involves creating patient-derived preclinical models, such as spheroid cultures and mouse xenograft models, to test new treatment strategies. Blood samples and tissue biopsies are collected during surgeries, biopsies, or diagnostic tests. Researchers use advanced molecular techniques like single-cell RNA sequencing to examine tumor heterogeneity and the liver environment, aiming to discover new biomarkers and treatment predictors. Participants will undergo procedures as part of their care, including hepato-bilio-pancreatic surgery, biopsies, or locoregional treatments. Blood samples are taken during these procedures to support research. Researchers will monitor surgery outcomes over an average of eight years. By studying patient samples and clinical data, the team aims to improve personalized medicine approaches and identify new preventive and therapeutic targets for chronic liver diseases and liver cancer.

Researchers are evaluating the use of 3D ultrasound imaging to guide standard care procedures such as ablation or biopsies of liver or kidney tumours. This observational study compares 3D ultrasound with conventional 2D ultrasound and checks the imaging results against pre- and post-procedure CT scans to assess how well tumours are removed or targeted during biopsies. The 3D ultrasound method uses a special assembly to move the ultrasound transducer in precise steps, creating detailed 3-dimensional images from multiple 2D images. During the study, patients undergoing liver or kidney tumour ablation or biopsy will be imaged using both standard care and 3D ultrasound devices. These devices record image data passively while the medical procedures are performed. The 3D ultrasound images are processed with specialized software to create volumes that allow viewing the area of interest from different angles. This imaging will be compared with CT images to verify the accuracy of tumour removal or biopsy targeting. Participants will be imaged by physicians during their scheduled ablation or biopsy procedures. The study involves collecting ultrasound image data during the treatment and analyzing these images afterward. Researchers will review the guidance and targeting accuracy of the needles used during these procedures as the primary outcome. The study is conducted by Western University, Canada, and patients who are well enough to consent and undergoing these standard care procedures are eligible to participate.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and a leading cause of cancer-related death worldwide, with poor median survival. In advanced stages, HCC often spreads beyond the liver to organs like lungs, bones, and lymph nodes. This research aims to assess the clinical impact of a new liver-specific PET tracer, 18F-FDGal, combined with PET/CT or PET/MRI scans, to improve diagnosis, staging, and evaluation of treatment response in patients suspected of or diagnosed with HCC. Participants suspected of or diagnosed with HCC will receive an initial diagnostic 18F-FDGal PET/CT or PET/MRI scan. Those undergoing loco-regional treatment such as surgery, ablation, or chemo-/radio-embolization will have follow-up scans at 1-2 months and 3-5 months after treatment. Experienced specialists will analyze these images to detect lesions and compare findings to other imaging methods. The study aims to enroll about 125 patients over five years. During the study, participants will undergo PET scans using the 18F-FDGal tracer to assess liver metabolic function and tumor characteristics. The main outcomes include measuring the sensitivity and specificity of 18F-FDGal PET imaging and evaluating liver function over five years. The study will monitor changes before and after treatment, helping to understand prognosis and treatment effects. Participation involves multiple imaging assessments and clinical evaluations throughout the study period.

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 developing advanced four-dimensional magnetic resonance imaging (4D-MRI) techniques to create detailed, moving images of the lungs and liver in adults. This imaging method produces three-dimensional movies that capture organ motion during breathing, which is important for improving radiation therapy planning for lung and liver cancer patients. The study aims to overcome challenges in current imaging methods to better target tumors that move with respiration. The study includes two main parts: technical development of ultra-quality 4D-MRI in healthy volunteers and evaluation of the technique in cancer patients. This involves creating a new MRI pulse sequence and image reconstruction process to achieve high spatial and temporal resolution with minimal motion artifacts. Researchers will compare the new 4D-MRI method to existing imaging and registration techniques in both healthy volunteers and patients with lung or liver tumors undergoing radiation therapy. Participants will undergo a single imaging session lasting up to two hours involving 4D-MRI scans. Healthy volunteers and cancer patients will be assessed to measure image quality and accuracy of motion modeling. The study will monitor how well the 4D-MRI technique captures tumor movement compared to current methods. The total participation time is limited to the imaging session, with no long-term follow-up mentioned.

Researchers are studying the effects of a drug called 177Lu-PSMA-617 in patients who have metastatic hepatocellular carcinoma (HCC), a type of liver cancer that is often advanced and cannot be surgically removed. This study focuses on patients whose tumors show positive uptake of prostate specific membrane antigen (PSMA), a protein found in tumor blood vessels and targeted for treatment. The trial aims to explore the potential of PSMA-targeted therapy in HCC, a disease with limited biomarker-directed options despite recent improvements from immunotherapy. Participants will receive intravenous infusions of 177Lu-PSMA-617 at a dose of 7.4 GBq (200 mCi) every six weeks. The treatment uses a radioligand approach, where the drug delivers targeted radiation to PSMA-positive tumor cells identified through special PET imaging. The study includes one main treatment arm and will monitor treatment effects and safety over time, with dosing repeated at six-week intervals. During the study, participants will undergo PSMA PET scans to confirm tumor uptake, and researchers will track side effects and treatment responses through imaging and laboratory tests. Outcomes measured include the percentage of participants with PSMA-positive lesions, safety and tolerability of the drug, progression-free survival, overall survival, and tumor response rates. The study will follow participants for several months to assess these outcomes and monitor long-term safety.

This clinical trial is studying patients with hypoalbuminemia and a new diagnosis of small, early-stage hepatocellular carcinoma (HCC). It aims to compare outcomes between two liver-directed treatments to see if 90-Yittrium Therasphere transarterial radioembolization (90Y) reduces the risk of disease progression within one year after diagnosis. The focus is on patients with a single tumor 3 cm or smaller and albumin levels below 3.4 g/dL at diagnosis. Participants are randomly assigned to receive either 90Y or microwave ablation (MWA) as their first liver-directed therapy. The 90Y treatment involves a two-phase process including a mapping angiogram with personalized dosimetry followed by infusion of 90-Yittrium glass microspheres targeting the tumor area. The MWA uses a high-powered, gas-cooled multi-antenna system to ablate the tumor with an ablative margin greater than 5 mm. After this initial treatment, participants continue with standard care for early-stage HCC. Throughout the study, participants are followed for one year after their first treatment cycle. Researchers will collect data on adverse events, treatment response, time to any retreatment, duration of response, and disease progression. The main measure is disease progression at one year, with additional evaluations done 60 to 120 days after treatment. This monitoring helps assess the safety and effects of the two treatments over time.

Researchers are evaluating the use of multiparametric dynamic whole-body [68Ga]Ga-PSMA PET/CT imaging in patients newly diagnosed with hepatocellular carcinoma (HCC) or those with recent suspicion of refractory, residual, or recurrent disease. The study aims to assess how this imaging technique performs diagnostically and to explore kinetic modeling in this patient population. Participants receive a dynamic whole-body [68Ga]Ga-PSMA PET/CT scan as the investigational procedure. This involves the administration of [68Ga]Ga-PSMA-11 as a radiation-based imaging agent. The study does not mention multiple treatment groups or comparators and focuses on detailed imaging acquisition and analysis. During the study, participants undergo imaging assessments at baseline and follow-up evaluations over six months to measure diagnostic performance, comfort during the procedure, and compare dynamic versus static imaging approaches. Researchers will collect kinetic parameters and evaluate the imaging results at both lesion and patient levels. The total study involvement includes baseline imaging and follow-up assessments within a six-month period to monitor outcomes and safety.

Researchers are evaluating super Hi-TCR-T cells targeting multiple proteins including Nectin4, NKG2DL, TROP2, B7H3, GPC3, and FAP for treating patients with advanced hepatocellular carcinoma (HCC) and other solid tumors that have not responded to prior treatments or cannot tolerate them. This prospective, single-arm clinical trial aims to assess the safety, tolerability, and effectiveness of this cell therapy, focusing on progression-free survival as a primary outcome. The study also explores quality of life, disease control rates, overall survival, and potential biomarkers related to therapy response. The treatment involves collecting peripheral blood lymphocytes from patients to prepare customized Hi-TCR-T cells targeting three selected proteins, including FAP. Patients undergo chemotherapy pretreatment with fludarabine and cyclophosphamide before receiving an intravenous infusion of these cells at a dose of 3.0 x 10^6 cells per kilogram of body weight for each target. As the disease progresses, the cell dose or target combination may be adjusted by a multidisciplinary team to improve efficacy. The study includes preparatory, recruitment and treatment, and data analysis phases spanning several months. Participants will undergo baseline assessments including physical exams, lab tests, imaging, and tumor marker evaluations before treatment. Safety monitoring occurs frequently after cell therapy at multiple time points up to 12 months, alongside efficacy evaluations at intervals up to 36 months post-treatment. Blood samples are collected periodically to study the persistence and expansion of the infused cells and their relation to disease changes. The study duration covers the treatment period plus follow-up until 12 months after the last patient's medication ends or other defined endpoints.