Simvastatin for Preventing Liver Cancer in Patients With Cirrhosis

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Statins, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Liver transplant, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

52 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

Yes, you will need to stop taking certain medications that interact with statins, such as gemfibrozil, cyclosporine, and others listed in the exclusion criteria. If you are currently using any of these, you cannot participate in the trial.

What data supports the effectiveness of the drug Simvastatin for preventing liver cancer in patients with cirrhosis?

Research shows that Simvastatin can improve outcomes for patients with liver cirrhosis by reducing inflammation and portal pressure, and it may also help prevent liver cancer by targeting specific liver cells and reducing tumor growth. ^{1 2 3 4 5}

Is simvastatin safe for people with liver cirrhosis?

Research shows that simvastatin is generally safe for people with liver cirrhosis, with studies indicating it can lower complications like portal hypertension and reduce mortality without significant adverse effects. ^{2 5 6 7 8}

How is the drug simvastatin unique in preventing liver cancer in patients with cirrhosis?

Simvastatin is unique because it not only lowers cholesterol but also targets liver sinusoidal endothelial cells to remodel the tumor environment, potentially improving outcomes in liver cancer. It also helps reduce inflammation and portal pressure in cirrhosis, which may prevent liver cancer development. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial studies if simvastatin can prevent liver cancer in patients with liver cirrhosis. Simvastatin, usually used to lower cholesterol, might block enzymes that cancer cells need to grow. The trial targets patients with liver disease. Simvastatin has been shown to reduce the risk of liver cancer and improve outcomes in these patients.

Research Team

Marc T Goodman

Principal Investigator

Northwestern University

Eligibility Criteria

Adults with liver cirrhosis who are not pregnant or breastfeeding, have not had a liver transplant or certain cancers, and do not drink excessively can join. They must be in fairly good health otherwise, with specific blood test results within acceptable ranges and able to use birth control if necessary.

Inclusion Criteria

Have had an abdominal imaging test (CT, MRI, or ultrasound) within the past 18 months

Platelets >= 50,000/microliter

Hemoglobin >= 8 g/dL

Exclusion Criteria

Model for end-stage liver disease (MELD) > 20

Any lab results that do not meet inclusion criteria after the Screen 1 blood tests

Women who are pregnant or breastfeeding; pregnant women are excluded from this study because simvastatin is a lipid-lowering agent with the potential for teratogenic or abortifacient effects; it is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with simvastatin, breastfeeding should be discontinued if the mother is treated with simvastatin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive simvastatin or placebo orally once daily for up to 6 months. Blood collection and CT/MRI scans are conducted throughout the trial.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 30, 60, and 90 days.

3 months

3 visits (in-person)

Treatment Details

Interventions

• Simvastatin

Trial Overview The trial is testing whether simvastatin can prevent liver cancer in patients with liver cirrhosis. Participants will either receive simvastatin or a placebo while undergoing regular monitoring through imaging tests like CT scans and MRIs, as well as providing biospecimens.

Participant Groups

Group I: Group I (simvastatin) Experimental Treatment 5 Interventions

Patients receive simvastatin PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood on study and CT/MRI throughout the trial.

Group II: Group II (placebo) Placebo Group 5 Interventions

Patients receive placebo PO QD. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood on study and CT/MRI throughout the trial.

Simvastatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in United States as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Canada as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Japan as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 30 patients with decompensated cirrhosis, simvastatin treatment for one year significantly reduced cirrhosis severity, particularly in patients who improved from Child-Pugh class B to A, indicating its potential efficacy in managing cirrhosis.

Patients who responded positively to simvastatin also experienced improved health-related quality of life and fewer hospitalizations for cirrhosis complications, suggesting that simvastatin may have beneficial anti-inflammatory effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients. Muñoz, AE., Pollarsky, F., Marino, M., et al.[2023]

Statins, commonly used for lowering cholesterol, are safe for patients with chronic liver disease and cirrhosis, and they may even reduce mortality and the risk of liver complications.

The review highlights that statins can help decrease complications in liver cirrhosis by addressing issues like portal hypertension, sepsis, and the risk of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety and Benefit of Statins in Liver Cirrhosis: a Review. Souk, K., Al-Badri, M., Azar, ST.[2015]

Statins, known for lowering cholesterol, also have beneficial effects in cirrhosis patients, including anti-inflammatory properties and potential to reduce the risk of liver complications and mortality, based on retrospective studies.

Ongoing clinical trials are expected to provide more insights into the safety and effectiveness of statins in treating cirrhosis, which could influence future treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging role of statin therapy in the prevention and management of cirrhosis, portal hypertension, and HCC. Sharpton, SR., Loomba, R.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Simvastatin is Efficacious in Treating Cirrhosis: A Meta-analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

The Safety and Benefit of Statins in Liver Cirrhosis: a Review. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of portal pressure by doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Emerging role of statin therapy in the prevention and management of cirrhosis, portal hypertension, and HCC. [2023]