Hepatoblastoma

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.

Researchers are conducting a Phase 3 multi-institutional study to treat children newly diagnosed with hepatoblastoma, a type of liver cancer. The study evaluates a modified Pediatric Hepatic International Tumor Trial (PHITT) strategy, including a randomized assessment of sodium thiosulfate (STS) to protect hearing in children with localized disease. It also investigates response-adapted therapy for patients with metastatic disease, aiming to improve event-free survival and assess treatment effects on hearing and tumor response. Children are divided into four groups based on tumor characteristics and treatment needs. Group A includes patients with tumors completely removed at diagnosis, receiving either no further chemotherapy or two cycles of cisplatin. Group B receives cisplatin monotherapy, with or without STS, and Group C receives a combination chemotherapy regimen, also with or without STS. Group D includes patients with metastatic disease who receive induction chemotherapy followed by response-adapted consolidation therapy. Surgery to remove tumors or pulmonary nodules is scheduled at specific times during treatment based on response. Participants will undergo regular assessments including audiograms to monitor hearing and evaluations of event-free survival for up to three years. Researchers will also monitor treatment-related side effects and tumor response. Tumor, blood, and urine samples will be collected for biological studies. The total participation time includes treatment cycles, surgery, follow-up evaluations, and up to three years of monitoring for outcomes and safety.

Hepatoblastoma is the most common malignant liver tumor in infants and young children, making up 65% of pediatric liver cancers under 15 years old. While early-stage patients have a survival rate above 90%, those with high-risk disease face survival rates around 40%, indicating a need for better treatments. Different definitions of high-risk hepatoblastoma exist internationally, and intensified chemotherapy regimens have shown improved survival but also increased side effects. This trial aims to find the best chemotherapy approaches for children with hepatoblastoma in China and to explore a new blood test for monitoring the disease. Participants will be grouped by risk level and receive tailored treatments. Very low-risk patients may have surgery alone or single-agent chemotherapy with cisplatin (DDP). Low-risk patients get 2 to 4 cycles of DDP chemotherapy before surgery and 2 cycles after. Intermediate-risk patients are randomized to either SIOPEL-3 HR chemotherapy or C5VD chemotherapy for 2 to 4 cycles, followed by surgery and additional chemotherapy to total 6 cycles. High-risk patients receive a combination chemotherapy regimen including C-CD, ICE, and sorafenib for 3 to 5 cycles, followed by surgery and total 6 to 7 chemotherapy cycles. Blood samples will be collected regularly to monitor a biomarker called 5hmc. During the study, participants will undergo staging, treatment cycles, elective surgery, and follow-up assessments. Researchers will monitor progression-free survival and overall survival over 24 months. The study includes collection of peripheral blood for epigenetic profiling to evaluate treatment response and detect recurrence. Safety and consistency of treatment outcomes will also be assessed. The total duration and detailed monitoring will help optimize therapies and improve future care for children with hepatoblastoma.

Researchers are investigating the use of 18F-DFA PET imaging to evaluate liver injury, a condition involving rapid liver function decline with symptoms like increased liver enzymes, jaundice, and abdominal discomfort. This observational study aims to assess how accurately this imaging method detects liver damage compared to standard clinical biochemical tests and liver biopsy, which is the current gold standard despite its sampling limitations. The study focuses on adults clinically diagnosed with liver damage or liver failure, exploring the correlation between 18F-DFA uptake in the liver and liver function indicators. Participants diagnosed with liver injury will undergo 18F-DFA PET imaging as part of the study. This radioactive tracer, based on vitamin C structure, is used to visualize liver function non-invasively. The imaging process involves a PET-CT scan lasting about 10 minutes, followed by a one-hour waiting period in the examination room before leaving. The study will compare imaging results with clinical liver function tests or liver biopsy findings to determine the sensitivity and specificity of this method. During the study, participants will have their liver function monitored using PET-CT scans and clinical biochemical markers. The primary outcomes include changes in liver uptake values on PET imaging at 6 months and the relationship between imaging results and standard liver function indicators. Participants will be followed up as needed, with assessments including liver enzyme levels and other blood tests. The total study duration depends on individual follow-up, and safety monitoring will address any issues related to PET imaging procedures.

Researchers are studying codrituzumab to see if it is a safe treatment with few or mild side effects for children and young adults aged 1 to 21 years who have solid tumors that express the protein GPC3 and have not responded to previous treatments or have had their cancer return. The study also aims to understand how codrituzumab is processed in the body, including absorption and clearance. This is a Phase I trial sponsored by Memorial Sloan Kettering Cancer Center focusing on relapsed or refractory extra-cranial solid tumors expressing GPC3. The study has two parts: Phase A uses a 3+3 design with two dose levels, starting at half the adult recommended dose and potentially increasing to determine the best pediatric dose. Phase B expands the study to include patients with hepatoblastoma. Participants will receive codrituzumab through weekly intravenous infusions over 21-day cycles and may continue treatment for up to 25 cycles if eligible. Dose escalation and safety will be closely monitored during the trial. Participants will be carefully evaluated before and during the study, including tumor measurements using RECIST 1.1 criteria, performance status assessments, and confirmation of GPC3 tumor expression. Researchers will estimate the maximum tolerated dose over one year and assess response rates at six weeks. Safety monitoring includes checking organ function and pregnancy status. Patients will be followed closely for side effects and treatment response throughout the study period lasting up to 25 treatment cycles.

Researchers are investigating the relationship between the volume of normal liver tissue removed during surgery, called resected normal liver parenchymal volume (RNLV), and the risk of liver failure after liver surgery (post-hepatetotomy liver failure, or PHLF). This observational study focuses on patients diagnosed with hepatocellular carcinoma (HCC) or intracholangiocarcinoma (ICC) who have undergone liver resection. The goal is to build and assess a personalized predictive model using RNLV to better estimate the risk of PHLF before surgery. The study collects data retrospectively from over a thousand patients treated at the investigator’s center. Patients are grouped based on whether they developed liver failure after surgery, defined by two sets of criteria known as the 50-50 criteria and ISGLS criteria. The research evaluates how well the RNLV-based model predicts PHLF and compares its usefulness to other methods, especially for patients with large or multiple liver tumors. Participants' medical records and surgical details are reviewed to calculate RNLV and assess liver failure outcomes within 30 days after surgery. The main outcome is the predicted probability of PHLF using the newly developed model. This approach aims to improve preoperative risk assessment to support safer liver surgeries. The study is sponsored by the National Natural Science Foundation of China and runs through the end of 2026.

Researchers are evaluating the tissue-agnostic effectiveness of the anti-PD1 antibody nivolumab in patients with advanced or metastatic rare tumors that express PD-L1 with a combined positive score of 10 or higher. This phase II basket trial includes patients whose cancers have progressed despite standard treatments. Rare tumors, defined by low incidence rates, collectively represent a significant portion of cancers with generally poor prognosis and limited clinical trial representation. Participants receive intravenous nivolumab at a dose of 480 mg every 4 weeks, continuing until disease progression, limiting toxicity, or for up to 12 months if responses are stable or improving. After treatment ends or discontinuation, patients are followed by phone every 60 days until death. This innovative approach targets the molecular characteristic PD-L1 regardless of tumor origin, aiming to provide new therapeutic options across many rare cancer types. During the study, researchers assess tumor response using RECIST v1.1 criteria and monitor biomarkers including PD-L1 expression, circulating tumor DNA, and microvesicles to understand treatment effects. Patients undergo regular evaluations to measure objective response and progression-free survival. Safety is closely monitored throughout the treatment and follow-up periods. The study is conducted across multiple centers to overcome challenges in rare cancer research and is expected to last about four years.

Researchers are evaluating the immune changes in tumors, blood, and bone marrow following the infusion of somatic cell therapy drugs in patients with solid tumors or hematologic cancers. The study aims to identify specific phenotypic, transcriptional, and epigenetic profiles of immune cells within tumors and correlate these profiles with clinical responses and potential toxicities. This research is designed to explore how different cellular components respond to adoptive cell therapy over time. Participants will undergo several procedures including three tumor biopsies taken at baseline, day 15, and optionally at relapse. Blood samples will be collected seven times at key intervals before and after treatment, including at day -7, day 0, day 3, day 7, day 15, month 3, and at relapse. If bone marrow biopsies or aspirations are done as part of routine care, additional samples will be taken for analysis. During the study, researchers will monitor immune cell changes using spectral flow cytometry and RNA sequencing three months after therapy infusion. They will also evaluate objective response at three months, and track progression-free and overall survival over five years. Safety of biopsy procedures will be assessed from enrollment until 30 days after the last sample. Participants are expected to comply with protocol requirements and provide informed consent, with total participation varying based on individual treatment and follow-up.

Researchers are evaluating how well pafolacianine works to identify cancerous lesions in children and adolescents with primary or metastatic solid tumors. This phase III trial focuses on using pafolacianine, a fluorescent imaging agent that targets folate receptors often found in many cancers. The agent is combined with near infrared (NIR) imaging during surgery to help locate tumor cells more effectively in pediatric patients with solid tumors. Participants receive an intravenous infusion of pafolacianine over 60 to 90 minutes before undergoing NIR fluorescent imaging during their planned standard of care surgery. During surgery, tissue samples are collected for analysis. This study involves only one experimental group using pafolacianine combined with NIR imaging to assist tumor detection during surgery. Throughout the trial, researchers monitor the accuracy of pafolacianine with NIR imaging in detecting lesions up to 30 days after surgery. They also measure the time between pafolacianine administration and imaging detection, reasons for not removing certain lesions, and any adverse events related to surgery. Participants are closely followed to assess safety and effectiveness of this imaging method as part of their surgical care.

This observational study focuses on liver transplant patients who are taking tacrolimus-containing medications. It aims to compare the pharmacokinetic parameters of different tacrolimus products and examine their relationships to liver function, kidney function (estimated glomerular filtration rate), and patient adherence. The study also monitors the occurrence of acute graft rejection and infections such as BK and cytomegalovirus during the observation period. This research addresses the lack of real-life data on immunosuppressive drug effectiveness and safety in liver transplant patients across Europe. Participants are liver or simultaneous liver-kidney transplant recipients aged 18 years or older who have been on tacrolimus-containing immunosuppressant therapy for at least four weeks before joining. Various tacrolimus medications, including Envarsus, Adport, Advagraf, Modigraf, Prograf, and Tacforius, are used under routine clinical care following local dosing guidelines. The study observes patients over a 24-month period without changing their prescribed treatments. During the study, participants undergo routine clinical visits and tests as part of their standard care, with no additional procedures required. Researchers collect data on tacrolimus blood levels, daily doses, and their variability, alongside liver and kidney function tests. Adherence is assessed using the BAASIS questionnaire and electronic health records of prescription fills. Outcomes such as graft rejection, infection rates, and drug tolerability are evaluated over 12 months, with ongoing monitoring for up to two years.