Active clinical trials for "Carcinoma, Hepatocellular"

The objective of this study is the acquisition of whole blood samples and serum samples from participants with untreated Hepatocellular Carcinoma (HCC) and subjects undergoing Hepatocellular Carcinoma (HCC) surveillance. These samples will be used for research purposes to develop and validate the Helio multi-analyte blood test.

The goal of this study is to create a data registry to capture clinical, pathologic, and molecular data/outcomes for patients with metastatic colorectal cancer who undergo live donor liver transplantation.

Hepatocellular carcinoma (HCC) is the 4th most common cause of cancer death globally but only 20% are diagnosed in its early stages where curative treatment can be carried out. Current standard-of-care surveillance of patients at high risk of developing HCC with 6-monthly serum alpha-fetoprotein (AFP) and ultrasound imaging (US) has a sensitivity of approximately 63% for detecting early HCC. There is an urgent need for a more efficacious and convenient modality of surveillance of high-risk patients to diagnose HCC at an early stage. In another study (AHCC10 ELEGANCE, NCT04965259), 2,000 patients at risk of developing HCC will be enrolled to develop the 1st miRNA in-vitro diagnostic (IVD) kit for HCC that has higher accuracy and better ease of use compared with the extant combination of AFP and US. This prospective study will act as a positive control to the AHCC10 ELEGANCE Study and aims to address the absence of efficacious modalities of surveillance by validating a panel of circulating miRNA biomarkers signatures with histologically proven HCC. This study will determine progressive changes in the profiles of miRNA signatures pre- and post- surgical resection to identify signatures predictive of recurrence. Additionally, this study also aims to identify changes in key metabolites and microbiome with correlation to changes in choline, bile acid and tryptophan metabolic pathways with changes in the composition and function of gut microbiota to establish actionable biomarkers that can predict HCC recurrence.

Liver transplantation is the standard treatment for patients with early-stage Hepatocellular Carcinoma (HCC). Currently, important treatment decisions, like the selection of patients for transplantation, are made on crude, static tumour characteristics such as the size and number of lesions that do not reflect other aspects of tumour biology. To date, pre-transplantation percutaneous biopsy is the best strategy to assess tumoral differentiation and, consequently, tumor biological behavior. Previous studies have demonstrated that 18F-Fluorodeoxyglucose Positron Emission Tomography Magnetic Resonance Imaging (18F-FDG PET/MRI) may have role in assessing the HCC tumoral differentiation and predict survival after LT. The Investigators will assess the accuracy of 18F-FDG PET/MRI as a tool to predict HCC recurrence after liver transplant. To understand the role of 18F-FDG PET/MRI in prediction of HCC's biological behavior and upon recurrence, the investigators will try to assess whether the findings in 18F-FDG PET/MRI can predict HCC poor tumoral differentiation, if the findings in 18F-FDG PET/MRI are related to presence of circulating tumoral DNA in plasma and try to determine the role of 18F-FDG PET/MRI in predicting HCC recurrence after resection. These findings may impact the selection criteria for liver transplantation.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. The combination of the ICI and other treatment regimens (Anti-VEGF, locoregional therapies et al) produced superior results in patients with advanced-stage HCC compared to those treated with traditional therapeutic regimens. Liver transplantation (LT) offers excellent long-term outcomes for certain patients with HCC. However, the immune-stimulating property of ICIs may lead to rejection and even graft loss, damping their use in treating HCC before liver transplantation. Therefore, it is worthwhile to explore the relationship between exposure to ICIs before LT and the incidence of graft rejection and rejection-related death or graft loss after LT.

Circulating tumor DNA (ctDNA) carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Hepatocellular carcinoma (HCC) specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Use of 'liquid biopsy' by assessing circulating cell free DNA enables the clinician to offer targeted immunotherapy or signaling pathway inhibitors. It also offers a model to prove response to locoregional or immunotherapy therapy and predict tumor recurrence non-invasively.

Since December 2019, a new disease named COVID-19 linked to a new coronavirus, SARS-CoV2 has emerged in China in the city of Wuhan, Hubei province, spreading very quickly to all 5 continents, and responsible for a pandemic. France is the third most affected country in Europe after Italy and Spain. Groups of patients at a higher risk of developing a severe form of COVID-19 have been defined: this include patients with immunosuppressive disease as cancer or patients with advanced cirrhosis of the liver. Coronavirus liver injury had been described with SARS-CoV 1 and MERS-CoV. There is no data on liver damage associated with COVID-19 infection for compensated or decompensated cirrhotic patients. The objectives of this project are to estimate the incidence of COVID-19 in hepatocellular carcinoma population, both hospital and ambulatory, and to study the impact on the frequency of severe forms, the prognosis, but also liver function, and the management of hepatocellular carcinoma, in this context of pandemic

This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC).

Recently, oncology has moved to a new clinical practice, more personalized, called Predictive Oncology (PO). PO comes from our knowledge about tumor heterogeneity that implies that each disease, thus each patient, is unique. PO's goal is to identify and administrate the right treatment to the right patient. For this, PO requires to go through 3 majors steps: A good characterization of the tumor to identify candidates, A well-established panel of drugs targeting the identified candidates, A relevant model to functionally test these candidates. The first point could easily be addressed with recent technologies that now allow the Next Generation Sequencing (NGS) and/or the simultaneous analysis of transcriptomic profiles from thousands of patients. The last two points have not been efficiently achieved so far, which prevents PO to be really efficient. Indeed, even if NGS allows the identification of potential targets, the presence of a molecular candidate does not necessary means obligatory functional response. The number of drugs approved by the Food and Drug Administration remains limited and most frequent targets in solid tumors (for ex. RAS, P53, MYC, RB1 ...) still do not have specific drugs approved in clinic. Finally, available pre-clinical models still present many major inconvenient: Chimiogrammes on 2D cultures are not sufficiently relevant to be really predictive of the in vivo situation; Patient derived xenograft (PDX) are not adapted for clinical use because not all tumors graft and the time to develop a PDX is too long (several months), thus incompatible with the history of the disease (especially for most severe patients). Furthermore the host (NOD-SCID mouse) is immuno-depressed, preventing to objectively test antibodies-mediated drugs. Recently, the 3D cell culture technology has proven its superiority to predict drug response over classical 2D chimiogrammes. It consists in growing "mini-tissues", or organoid-derived from tumor/healthy tissues, thanks to the amplification of stem cells contained within the sample. The generated organoids are personalized and biologically relevant (organoids are expend form the patient's stem cells which self-organized according to the architecture of the tissue they are originating from), they are genetically stable, their growth is compatible with patient's disease history (organoids grow in few weeks), easy and convenient to achieve, even from small biological material quantities (0.5< x < 1cm3), and they can be amplified, frozen and thawed on demand. Moreover, organoids can be made more complex with the addition of other cell types (fibroblasts, immune cells …). None of the actual available pre-clinical model regroups all these characteristics. The constitution of a "next generation" biobank of liver samples (Metastases to the liver and Hepato Cellular Adenocarcinoma) will be very useful in the context of predictive oncology. For this, a biopsy needs to be dissociated and grown in Matrigel™, in presence of a well-defined list of growth factors. Once the culture is established, organoids can be frozen then defrost on demand. Our main objective is to evaluate the feasibility for building a biobank of liver-derived organoids, from liver metastases of colorectal cancers, hepatocellular adenoma and adenocarcinoma (waste tissues). Applications related to organoids derived from tumors are quasi indefinite, from drug screening assays, tests for novel therapies or original drug combinations, to patients' stratifications or fundamental research. In our case, we are interested in building this a biobank in the prospect of using it to build the "next generation of model for predictive oncology" to study liver-related cancers and related drugs testing. Briefly, we want to implement these organoids with cells from the microenvironment in order to makes the global model more pertinent for drug testing. If successful, the generation of such biobank, including both tumor-derived organoids and healthy counterpart, could be really helpful for the scientific and medical community.

In summary, with the help of single-cell sequencing technology, this study aims to focus on elucidating the influence of HBV-induced hepatocellular carcinoma cell metabolic changes on microenvironment remodeling. With the help of hepatocellular carcinoma microenvironment changes, this study provide a more accurate diagnosis and treatment method for HBV-induced hepatocellular carcinoma.