View clinical trials related to Carcinoma, Hepatocellular.
Filter by:Hepatocellular carcinoma is the most common type of liver cancer, which is the 3rd leading cause of cancer deaths worldwide. The incidence is expected to increase as a consequence of chronic liver disease with its multiple risk factors, including chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, excessive alcohol consumption, nonalcoholic fatty liver disease, hemochromatosis, and aflatoxin B1.It is estimated that 70%-90% of patients with HCC have chronic liver disease and cirrhosis, which limits the feasibility of surgical procedures in advanced cases. There are limited treatment options for HCC patients who are ineligible for surgical resection. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolization (TACE), transarterial embolization (TAE), or hepatic arterial infusion chemotherapy (HAIC), are primarily recommended, and if one of those fail, then systemic therapy is considered. The 2013 Japan Society of Hepatology HCC Guidelines outlined that the factors influencing treatment decisions should be based on the degree of liver damage (Child-Pugh), presence or absence of extrahepatic spread and macrovascular invasion, the number of tumors, and tumor diameter. Sorafenib has been the standard of care since 2007, when the SHARP trial demonstrated that sorafenib improved median overall survival (OS) compared to placebo in patients who had not received prior systemic therapy (10.7 vs 7.9 months, HR =0.69, P<0.001). In patients from the Asia-Pacific region taking sorafenib, the median improvement in overall survival compared with placebo was 2.3 months (6.5 months vs 4.2 months; HR 0.68; p=0.014). Drug development for hepatocellular carcinoma in the past 10 years has been marked by four failed global phase 3 trials (of sunitinib, brivanib, linifanib, and erlotinib plus sorafenib) that did not show non-inferiority. Sorafenib, an oral multikinase inhibitor, has been the only systemic therapy demonstrated to extend overall survibility as a firstline treatment, showing a median improvement of 2.8 months compared with placebo (10.7 months vs. 7.9 months; hazard ratio [HR] 0.69; p\0.001).6 Inpatients from the Asia-Pacific region taking sorafenib, the median OS (mOS) improvement compared with placebo was 2.3 months (HR 0.68; p = 0.014). The use of other molecularly targeted agents has not demonstrated efficacy via non-inferiority or superiority to sorafenib; thus, until the appearance of lenvatinib, sorafenib has also been widely used as the first-line treatment for uHCC patients in Japan. Recently, regorafenib and Nivolumab were approved as a second-line systemic treatment for patients who do not respond to the first-line treatments. Otherwise, best supportive care or participation in clinical trials is recommended in the second-line setting by treatment guidelines. Chemotherapy in combination with sorafenib (doxorubicin) and radioembolization with SIR Spheres Y-90 resin microspheres failed to demonstrate a survival benefit or showed a worse safety profile compared to sorafenib in the first-line setting. Eventually, the PhaseIII non-inferiority REFLECT trial showed that lenvatinib was non-inferior compared to sorafenib.
Cohort study to assess the impact of ctDNA detection in the follow-up and management of patients with hepatocellular carcinoma treated by TACE
This is an open-label, multi-center, single-arm, phase II study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab as a neoadjuvant therapy in subjects with resectable 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: 1. A good characterization of the tumor to identify candidates, 2. A well-established panel of drugs targeting the identified candidates, 3. 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.
To observe and explore the effect of anti-angiogenesis combined with PD-1/PD-L1 therapy in the real world on the survival prognosis of patients with advanced liver cancer, and to summarize the treatment experience of a wide range of people.
This is a multi-national, phase II, parallel-arm, double-blind, placebo-controlled, two-arm study designed to assess the efficacy and safety of SIRT-Y90 followed by atezolizumab plus bevacizumab [study arm], versus SIRT-Y90 followed by placebo [control arm] in patients with locally advanced Hepatocellular Carcinoma (HCC).
BACKGROUND It is estimated that around 71 milion people live with chronic hepatitis C virus (HCV) infection. This may lead to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Liver cirrhosis is considered as one of the most common risk factors of hepatocellular carcinoma (HCC). HCC is seventh most common cancer worldwide. The treatment of HCV with direct-acting antivirals (DAAs) has led to the increase of sustained virological response (SVR) rates to more than 90%. It is suggested that the virus eradication reduces, but not eliminates the risk of HCC. This concerns especially patients with liver cirrhosis or previous HCC history. There are reports of early occurrence of HCC after the DAA treatment. Therefore, patients undergoing successful HCV treatment should be monitored for the possibility of hepatoccelular carcinoma occurrence. AIM OF THE STUDY In this study the investigators aimed to assess the occurrence of HCC after direct acting antiviral HCV treatment and evaluate whether the course of HCC and liver function differ among the population of patients treated with DAAs and those who were not receiving the therapy with DAA. MATERIAL AND METHODS This is the observative, cohort, retrospective study which will be performed in several clinical centres in Poland. The inclusion criteria are: hepatocellular carcinoma diagnosis, age >18 years old. The investigators will collect both epidemiological (age, gender, comorbidities, alcohol abuse) and clinical data (serum bilirubin, alanine, aspartate aminotransferase, platelets, gammaglutamyltransferase, alkaline phosphatase and alpha-fetoprotein level, Child-Pugh and MELD score, imaging tests, liver biopsy and elastography, if performed). In all patients, the HCV infection and co-infections will be assessed. In those who underwent the DAA treatment, the composition of the therapy and response to the treatment will be evaluated. Statistical analysis will be performed in subgroups of patients undergoing DAA treatment and without the therapy. The distribution of continuous variables will be analysed by the Shapiro-Wilk test. Quantitative data will be analysed using the Mann-Whitney U test or Kruskal-Wallis ANOVA when appropriate. Qualitative data will be compared using the χ² test or the Fisher exact test. Correlations between quantitative variables will be assessed using the Spearman correlation coefficient. P value will be set at <0.05. FUNDING: No remuneration is provided for participation in the study
This is a first-in-human, Phase 1 open-label, multicenter, dose escalation, safety, pharmacodynamic, and PK study of exoASO-STAT6 (CDK-004) in patients with advanced Hepatocellular Carcinoma (HCC) and patients with liver metastases from either primary gastric cancer or colorectal cancer (CRC).
The goal of the REMNANT study is to confirm the clinical value of detecting a new biomarker, ctDNA (circulating tumor DNA), in the follow-up of patients with operated liver cancer. In order to meet this objective, this biomarker will be measured in your blood before and after surgery, at three and six months.
Liver cancer is one of the most common malignant tumors worldwide with high morbidity and mortality, and hepatocellular carcinoma (HCC) is the main histological subtype. So far, liver resection is the most effective treatment but the postoperative recurrence rate is high at five years, and the prognosis is difficult to estimate. Microvascular invasion (MVI) and postoperative minimal residual disease (MRD) are crucial prognostic factors for patients undergoing hepatectomy. Although many laboratory and imaging methods have been established to estimate the recurrence risk, their stability and accuracy are still not high. To date, no unified conclusion is achieved. It's eagerly to screen out a batch of individualized staging and prognosis-related biological indicators for early warning and prediction of prognosis, having good stability and high precision. Circulating cell-free DNA (cfDNA) molecular detection technology is an emerging detection technology of tumor gene profiling in recent years, which can be used to predict and monitor tumor recurrence. In this study, by detecting genomic chromosomal abnormalities in plasma and tumor tissues of patients before and after surgery, the investigators hope to construct a preoperative MVI prediction model and a postoperative MRD monitoring model, so as to provide reference for the precise treatment of HCC.