Neoplasms

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Lipid Regulating Agents

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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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence	NCT03219372	Hepatocellular ... Liver Cirrhoses	Pravastatin Pil... Placebo Oral Ta...	18 Years -	Cedars-Sinai Medical Center
Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence	NCT03219372	Hepatocellular ... Liver Cirrhoses	Pravastatin Pil... Placebo Oral Ta...	18 Years -	Cedars-Sinai Medical Center

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