Simvastatin for Preventing Liver Cancer in Patients With Cirrhosis

Not currently recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether simvastatin, a common cholesterol-lowering drug, can prevent liver cancer in individuals with liver cirrhosis. The aim is to determine if simvastatin can inhibit cancer cell growth by blocking certain necessary enzymes. Participants will take either simvastatin or a placebo (a harmless pill without the drug) for up to six months. Individuals with a confirmed diagnosis of liver cirrhosis who have not used statins before and do not have certain medical conditions or medication conflicts may be suitable for this trial. As a Phase 2 trial, this research measures simvastatin's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

Is there any evidence suggesting that simvastatin is likely to be safe for humans?

Research has shown that simvastatin is usually safe for people with liver issues. One study with 30 patients who had a milder form of liver cirrhosis found that taking 40 mg of simvastatin improved liver blood flow without causing major side effects. Other studies have found that simvastatin can help people with liver cirrhosis, particularly with issues like bleeding in the digestive tract due to liver disease.

Importantly, these studies have not reported severe side effects for patients taking simvastatin, suggesting its relative safety for those with liver problems. However, discussing any concerns with a healthcare provider before starting new treatments is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about simvastatin for preventing liver cancer in patients with cirrhosis because it offers a unique approach compared to the current standard treatments like surveillance and antiviral therapies. Unlike these options, simvastatin is primarily known for its cholesterol-lowering effects but is being explored for its potential anti-cancer benefits, possibly due to its role in inhibiting cancer cell growth pathways. This dual-action mechanism means simvastatin could not only help manage cholesterol levels but also provide a new line of defense against liver cancer, making it a promising candidate for patients with cirrhosis.

What evidence suggests that simvastatin might be an effective treatment for preventing liver cancer in patients with cirrhosis?

Research has shown that simvastatin, which participants in this trial may receive, might help lower the risk of liver cancer. Studies indicate that people taking statins, such as simvastatin, have about a 26% lower chance of developing hepatocellular carcinoma, a common type of liver cancer. One study found that simvastatin significantly reduced liver scarring, known as cirrhosis, in patients over a year. Regular statin use is also associated with a 15% lower risk of developing new liver disease and a 28% lower risk of dying from liver-related causes. These findings suggest that simvastatin could effectively help prevent liver cancer in patients with liver cirrhosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Marc T Goodman

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02968810

NCT02968810 | Simvastatin in Preventing Liver Cancer in ... Study Overview. This phase II trial studies how well simvastatin works in preventing liver cancer in patients with liver cirrhosis. Simvastatin may stop the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6696599/

Statins and Hepatocellular Carcinoma Protection - PMC According to the most conservative estimate by this group of researchers, receipt of any statin was associated with an approximately 26% reduction in HCC risk.

3. withpower.com withpower.com/trial/phase-3-liver-cirrhosis-5-2017-9065f

Simvastatin for Preventing Liver Cancer in Patients With ... In a study of 30 patients with decompensated cirrhosis, simvastatin treatment for one year significantly reduced cirrhosis severity, particularly in patients ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2806370

Statin Use and Risk of Liver Disease, Hepatocellular ... Regular use of statins was associated with a 15% lower hazard ratio of new-onset liver disease and a 28% lower hazard ratio for liver-related deaths compared ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8422958/

SACRED: Effect of simvastatin on hepatic decompensation ... Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5822686/

Use of Statins in Patients with Chronic Liver Disease and ... In a study including 30 compensated cirrhotic patients, acute infusion of 40 mg of simvastatin showed an increase in hepatic blood flow and decreased hepatic ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2829933

Simvastatin and Rifaximin in Decompensated Cirrhosis Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis. Objective To assess whether simvastatin combined with rifaximin ...

8. journals.lww.com journals.lww.com/ajg/fulltext/9900/simvastatin_addition_to_standard_of_care_improves.1870.aspx

Simvastatin Addition to Standard of Care Improves Long- ... Simvastatin may be associated with improved survival in selected patients with cirrhosis after variceal bleed and reduced incidence of new onset ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1551714421001038

Effect of simvastatin on hepatic decompensation and death ... Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage ...

10. gastrojournal.org gastrojournal.org/article/S0016-5085(09)00144-9/fulltext

Simvastatin Lowers Portal Pressure in Patients With ... In that regard, recent data have shown that large doses of pravastatin are safe in patients with chronic liver disease.