Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Liver Cirrhosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fibrosis

Disease Attributes

Lipid Regulating Agents

All Drugs and Chemicals

Pravastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Enzyme Inhibitors

Pravastatin Pill

Placebo Oral Tablet

Shehnaz Hussain, PhD

Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will survive 5 years or more. While locoregional therapies are utilized in an effort to combat this disease, the recurrence rate of HCC after these therapies are high.

Statins are widely used drugs that lower cholesterol levels. Some studies have suggested that statins lower risk of HCC recurrence, but this possibility has not been studied thoroughly in a clinical trial. This study will examine the effects of pravastatin, a type of statin, on time to HCC recurrence in patients with early stage HCC. It is possible that pravastatin in combination with locoregional therapies may delay or protect against HCC recurrence.

To date, there has been a scarcity of clinical trials evaluating the effectiveness of adjuvant therapies in patients with early stage HCC, although it is widely considered an area of highly unmet need.

The objective of this randomized double-blinded, placebo-controlled Phase II trial is to examine the effects of pravastatin use versus placebo after 12 months of treatment on hepatocellular cancer (HCC) recurrence in 130 patients with liver cirrhosis, HCC meeting Milan Criteria or OPTN tumor downstaging criteria for tumor burden, and initial locoregional therapy (LRT) with adequate response.

Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence

Mean difference in time (in months) from baseline (study visit 1) to first hepatocellular cancer (HCC) recurrence or HCC death within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

- HCC recurrence will be confirmed by central expert independent radiographic review.

Mean difference in time (in months) from baseline (study visit 1) to first occurrence of a documented hepatocellular cancer (HCC) recurrence within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

- HCC recurrence will be confirmed by central expert independent radiographic review.

Mean difference in time (in months) from baseline (study visit 1) to death (for any reason) within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

Mean difference in time from baseline (study visit 1) to liver transplant waitlist drop-off within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

Mean difference in mean change in liver stiffness (as measured by MRE or FibroScan) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

Mean difference in within-person change in liver fat fraction (as measured by MRE) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

Mean difference in serum biomarkers including cytokines, chemokines, soluble receptors, and proteins (eg. IL6, TNFα, sTNFRII, IL18BP, sCD163, IL10, IL17, IL-8, CCL17, TGFβ) from baseline (study visit 1) to 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

Mean difference in liver tissue markers related to HCC including those in the Wnt/β-catenin pathway (eg. β-catenin, glutamine synthetase) from baseline (study visit 1) to 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Cedars-Sinai Medical Center

Associate Professor

Regular investigator assessment, regular laboratory testing, self-reporting.

Pravastatin 40 mg, daily for 12 months

Pravastatin, a lipid-lowering agent, is a derivative of ML236B (compactin), which was identified in a fungus called Penicillium citrinum in the 1970s. It is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.

Placebo identical in color, consistency, and appearance to pravastatin 40 mg, daily for 12 months

Placebo: A substance that has no therapeutic effect, and will be used as a control in testing the study agent.

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

0 participants enrolled in placebo group due to 1 total participant enrollment in pravastatin group.

Accrual fell well below target. One subject was randomized to the study and withdrew prior to completion. Outcome measures were not analyzed due to insufficient accrual.

Shehnaz K. Hussain, PhD, ScM

As accrual fell far below target, for associated privacy considerations related to the potential for participant re-identification, data are not reported.

Time to Recurrence

Recurrence Free Survival

Overall Survival

Waitlist Drop-off

Change in Liver Stiffness

Change in Liver Fat Fraction

Change in Serum Biomarkers of Monocyte/Macrophage and Stellate Cell Activation

Levels of Liver Tissue Markers Related to HCC

Overall Study

Patients with high risk of HCC having suspicious lesions with Diameters ≤ 2cm will receive CEUS and EOB-MRI examinations.

Diagnostic CEUS and EOB-MRI

Xiang Jing, MD

HCC is a serious threat to the health of people. Accurate diagnosis of early HCC by imaging allows patients to obtain proper treatment. However, for lesions with diameters ≤2 cm, the tumor blood supply is not fully established, and there may be no typical manifestation on the image. In addition, atypical enhanced patterns caused by liver cirrhosis may also hinder imaging diagnosis of HCC. Therefore, early diagnosis of HCC in the context of cirrhosis remains a major clinical problem.

Contrast-enhanced Ultrasound (CEUS) and MRI Contrast-enhanced Magnetic Resonance Imaging (CEMRI) are common diagnostic imaging methods. Till now, there is still lack of a detailed investigation comparing the diagnostic efficacies of CEUS and EOB-MRI for micro HCC in the context of cirrhosis. Therefore, this study aims to analyze the imaging patterns in CEUS and EOB-MRI for liver lesions with diameters ≤ 2 cm among patients with high risk of HCC, and to compare the diagnostic efficacies of EOB-MRI and CEUS for early-stage HCCs.

Comparing the Diagnostic Efficiencies of CEUS and EOB-MRI in Patients With High Risk of HCC

A Single-Center, Prospective Study Comparing the Diagnostic Efficiencies of Contrast-Enhanced Ultrasound and EOB Contrast-Enhanced Magnetic Resonance Imaging for Lesions With Diameters ≤ 2cm in Patients With High Risk of HCC

The sensitivity, specificity and accuracy of CEUS and EOB-MRI for liver lesion ≤ 2 cm will be calculated.

The sensitivity, specificity and accuracy of combined CEUS and EOB-MRI for liver lesion ≤ 2 cm will be calculated.

Tianjin Third Central Hospital

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Hematinics

Liver Extracts

Study the prevalence of cirrhosis in patients with VADS cancer

Evaluation of the hepatic fibrosis stage by a hepatological assessment (Clinical, biological and imaging)

Evaluation of the hepatic fibrosis

Cyril PAGE, PhD

Tobacco and alcohol are the two major risk factors for upper respiratory tract cancer (VADS).

Tobacco and alcohol are the two major risk factors for upper respiratory tract cancer (VADS). Among patients with VADS cancer, more than 60% reported daily alcohol consumption of more than 20 g / d. Such poisoning can be harmful, causing histological lesions of alcoholic liver disease, such as steatosis, alcoholic hepatitis, liver fibrosis and cirrhosis. In a population consuming more than 50 g of alcohol per day for 5 years, the prevalence of severe hepatic fibrosis is between 30% and 40%. In the therapeutic management of a cancer of VADS, the presence of cirrhosis is a prognostic element, increasing the postoperative risk of haemorrhage, surgical site infection and acute renal failure. The search for cirrhosis in the pre-therapeutic assessment is therefore important. The diagnosis of cirrhosis is not a problem when clinical, biological, radiological or endoscopic signs of hepatic insufficiency or portal hypertension are present. Asymptomatic cirrhosis is more difficult to diagnose without liver biopsy. Noninvasive hepatic exploration techniques have recently been developed and validated for the evaluation of liver fibrosis in the context of alcoholic liver disease. Fibroscan® (Echosens, Paris, France) is an imaging device for measuring the liver hardness (hepatic elasticity expressed in kPa), with a strong correlation with the presence of histological fibrosis of the liver. At the threshold of 19.5 kPa, Fibroscan can be used to diagnose cirrhosis with good diagnostic performance (Se 80%, Sp 90%, VPP 93%, VPN 70%) and good inter- and intra-observer reproducibility. Elastometry is a simple, reliable and non-invasive tool to systematically evaluate hepatic fibrosis in patients with VADS cancer. The examination can be performed during a routine care consultation. The post-therapeutic morbidity induced by cirrhosis in the cancers of VADS is not well known and there is no recommendation in France about the hepatic explorations to be carried out during the initial assessment of these neoplasias. It is essential to be able to specify this morbidity in order to adapt if necessary the therapeutic strategy of cancers of VADS.

The objective of this study is to systematically determine the presence of cirrhosis and / or liver fibrosis in patients with VADS cancer, in order to investigate their impact on the morbidity after treatment of squamous cell carcinomas of the head and neck.

Prevalence of Liver Fibrosis and Cirrhosis in Patients With Squamous Cell Carcinoma of the Head and Neck

Determine the prevalence, by registry data analysis, of cirrhosis in patients with VADS cancer

Centre Hospitalier Universitaire, Amiens

Patients with high risk of HCC having suspicious lesions on US will receive Sonazoid-CEUS and EOB-MRI examinations.

Diagnostic Sonazoid-CEUS and EOB-MRI

Yan Zhou

Hepatocellular carcinoma (HCC) is the fifth most common cancer. Patients with HCCs usually have a poor prognosis. Hepatocarcinogenesis is an intricate and multistep process. Detecting and staging early HCC in patients with liver cirrhosis are still challenging for imaging techniques. Contrast-enhanced ultrasonography (CEUS) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) are widely used in clinical practice. EOB-MRI has advantages of high detecting rate for small lesions, high sensitivity of hepatobiliary phase and extensive image information. Sonazoid has the advantage of offering a unique post-vascular phase, also called the Kupffer phase. Therefore, malignant tumors with few or no Kupffer cells appear as contrast defects, with respect to the relatively well-enhanced surrounding liver in the postvascular phase. The diagnostic efficacies of these two imaging methods have not been well studied. Therefore, the purpose of this study is to compare the efficacies of Sonazoid-CEUS and EOB-MRI in patients with high risk of HCC, and to compare the detection ability for malignant tumors by Kupffer phase and hepatobiliary phase.

Diagnostic Efficacies of Sonazoid-CEUS and EOB-MRI in Patients With High Risk of HCC

A Single-center, Prospective Controlled Study of the Diagnostic Efficacies of Sonazoid-CEUS and EOB-MRI in Patients With High Risk of HCC

The sensitivity, specificity and accuracy of Sonazoid-CEUS and EOB-MRI in the diagnosis for patients with high risk of HCC will be determined.

The detection rate of the additionally found HCC on Sonazoid-CEUS and EOB-MRI will be determined .

Anticoagulants

Nitric Oxide Donors

Micronutrients

Bone Density Conservation Agents

Vasodilator Agents

Respiratory System Agents

Edetic Acid

Pentetic Acid

Diethylenetriamine

Antidotes

Protective Agents

Chelating Agents

Iron

Iron Chelating Agents

Calcium

Calcium, Dietary

Nitric Oxide

This is a single arm study in which all participants have one ultrasound and one abbreviated MR exam

This study involves an on-label use of Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for the ....

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid

Alexandra Schlein

Yesenia Covarrubias

Claude B Sirlin, MD

This study compares gadolinium contrast-enhanced Abbreviated MRI (AMRI) to standard ultrasound for Hepatocellular Carcinoma (HCC) screening and surveillance in subjects with liver cirrhosis.

Ultrasound (US) is currently used for HCC surveillance. However, US has certain limitations, so physicians use contrast CT or MRI. However, these are expensive and time-consuming procedures. We introduced an abbreviated MRI (AMRI) exam, which works well in cirrhotic and obese patients (unlike US), involves no ionizing radiation (unlike CT), and is rapid (unlike multi-phasic MRI) with total scanner times of less than ten minutes, and can be performed at about the same cost as US. This study in adult patients with cirrhosis will compare the performance of AMRI vs. US for detection of early-stage disease, and will help to define and validate a novel, rapid, accurate, and potentially cost-effective imaging protocol for HCC screening in high-risk individuals.

Gadolinium Contrast-enhanced Abbreviated MRI (AMRI) vs. Standard Ultrasound for Hepatocellular Carcinoma (HCC) Surveillance in Patients With Cirrhosis

Abbreviated MRI (AMRI) vs. Ultrasound for HCC Surveillance in Cirrhosis

per-patient sensitivity, specificity, positive predictive (PPV), negative predictive value (NPV) and accuracy of full AMRI vs. simulated unenhanced AMRI vs. US for HCC screening

the inter- and intra-reader reliability of full AMRI vs. simulated unenhanced AMRI vs. US for HCC screening

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence	NCT03219372	Hepatocellular ... Liver Cirrhoses	Pravastatin Pil... Placebo Oral Ta...	18 Years -	Cedars-Sinai Medical Center
Comparing the Diagnostic Efficiencies of CEUS and EOB-MRI in Patients With High Risk of HCC	NCT04212286	Hepatocellular ... Liver Cirrhoses Diagnoses Disea...	Diagnostic CEUS...	18 Years - 80 Years	Tianjin Third Central Hospital
Prevalence of Liver Fibrosis and Cirrhosis in Patients With Squamous Cell Carcinoma of the Head and Neck	NCT03139058	Liver Fibroses Liver Cirrhoses Squamous Cell C...	Evaluation of t...	18 Years -	Centre Hospitalier Universitaire, Amiens
Diagnostic Efficacies of Sonazoid-CEUS and EOB-MRI in Patients With High Risk of HCC	NCT04212273	Hepatocellular ... Liver Cirrhoses Diagnoses Disea...	Diagnostic Sona...	18 Years - 80 Years	Tianjin Third Central Hospital
Gadolinium Contrast-enhanced Abbreviated MRI (AMRI) vs. Standard Ultrasound for Hepatocellular Carcinoma (HCC) Surveillance in Patients With Cirrhosis	NCT04288323	Liver Cancer Liver Cirrhoses Liver Carcinoma	Gadolinium etho...	18 Years -	University of California, San Diego
Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence	NCT03219372	Hepatocellular ... Liver Cirrhoses	Pravastatin Pil... Placebo Oral Ta...	18 Years -	Cedars-Sinai Medical Center
Comparing the Diagnostic Efficiencies of CEUS and EOB-MRI in Patients With High Risk of HCC	NCT04212286	Hepatocellular ... Liver Cirrhoses Diagnoses Disea...	Diagnostic CEUS...	18 Years - 80 Years	Tianjin Third Central Hospital
Prevalence of Liver Fibrosis and Cirrhosis in Patients With Squamous Cell Carcinoma of the Head and Neck	NCT03139058	Liver Fibroses Liver Cirrhoses Squamous Cell C...	Evaluation of t...	18 Years -	Centre Hospitalier Universitaire, Amiens
Gadolinium Contrast-enhanced Abbreviated MRI (AMRI) vs. Standard Ultrasound for Hepatocellular Carcinoma (HCC) Surveillance in Patients With Cirrhosis	NCT04288323	Liver Cancer Liver Cirrhoses Liver Carcinoma	Gadolinium etho...	18 Years -	University of California, San Diego

Spots Global Cancer Trial Database for liver cirrhoses