Atorvastatin for Liver Cancer Risk in Fibrosis

(TORCH Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Raymond Chung, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Raymond Chung

Must not be taking: Statins

Disqualifiers: HIV, Untreated HCV, Uncontrolled HBV, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Prospective randomized, multi-center, double blind placebo-controlled trial to assess the chemopreventive impact of atorvastatin (20 mg oral) vs placebo in up to 60 adults with advanced fibrosis at high risk of developing HCC.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but if you are taking a statin, you must stop it and undergo a 90-day washout period before starting the trial.

What data supports the idea that Atorvastatin for Liver Cancer Risk in Fibrosis is an effective drug?

The available research shows that Atorvastatin, a type of statin, is effective in reducing the risk of liver cancer in people with liver diseases. One study found that statin use, including Atorvastatin, was linked to a 44% reduction in the development of liver scarring and a 49% reduction in new liver cancer cases among patients with hepatitis C. Another study highlighted that Atorvastatin was particularly effective in reducing high-risk patterns associated with liver cancer development. These findings suggest that Atorvastatin is a potent option for lowering liver cancer risk in patients with viral and metabolic liver diseases. ^{1 2 3 4 5}

What safety data exists for atorvastatin in liver cancer risk and fibrosis treatment?

Atorvastatin is generally well tolerated, but there are concerns about hepatotoxicity, with some cases of liver injury reported. Statins, including atorvastatin, have been associated with idiosyncratic liver injury in 1.9%-5.5% of patients. Most patients recover after stopping the drug, though there have been rare cases of severe liver injury. Despite these risks, statins are being studied for their potential benefits in liver conditions, including cirrhosis and hepatocellular carcinoma prevention. ^{1 6 7 8 9}

Is the drug Atorvastatin a promising treatment for reducing liver cancer risk in people with liver fibrosis?

Yes, Atorvastatin shows promise in reducing liver cancer risk, especially in patients with liver diseases like hepatitis C and nonalcoholic fatty liver disease. It has been associated with a lower risk of developing liver cancer and slowing down liver damage. ^{2 3 6 10 11}

Research Team

Raymond Chung, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults over 18 with advanced liver fibrosis or cirrhosis at high risk for developing liver cancer (HCC) can join. They must be able to take medication as directed and complete study visits. Women who can have children must use birth control, and participants need recent liver imaging. People with other major illnesses, certain chronic liver diseases, uncontrolled infections like HIV or hepatitis B, a history of drug abuse, or those on statins recently cannot join.

Inclusion Criteria

I can follow the medication schedule and attend all study visits.

The subject must be able to comply with the instructions for taking the study drug and be able to complete the study schedule of assessments.

My scans show a liver condition with increased blood pressure in the portal vein.

Exclusion Criteria

ALT > 10 x ULN

Known positivity for HIV infection

I have been diagnosed with a chronic liver disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin or placebo daily for 48 weeks to assess chemopreventive impact on HCC risk

48 weeks

Regular visits every 4 weeks, with additional visits at weeks 12, 24, 36, and 48

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a 5-year observational study to examine HCC incidence

5 years

Treatment Details

Interventions

• Atorvastatin (Statins)
• Placebo (Placebo)

Trial Overview The trial is testing if Atorvastatin (20 mg daily pill) prevents liver cancer better than a placebo in people with serious scarring of the liver due to disease. It's a controlled test where neither doctors nor patients know who gets the real medicine versus a fake pill to ensure unbiased results.

Participant Groups

Group I: Group A: Atorvastatin 20 mg Experimental Treatment 1 Intervention

Atorvastatin 20mg will be administered daily via oral route for 48 consecutive weeks on an outpatient basis.

Group II: Group B: Placebo to Match (PTM) Placebo Group 1 Intervention

PTM will be administered daily via oral route for 48 consecutive weeks on an outpatient basis.

Atorvastatin is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Texas Southwestern Medical Center Dallas, TX

Massachusetts General Hospital Boston, MA

Who Is Running the Clinical Trial?

Raymond Chung

Lead Sponsor

Trials

3

Patients Recruited

100+

University of Texas Southwestern Medical Center

Collaborator

Trials

1102

Patients Recruited

1,077,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis. Kaplan, DE., Serper, MA., Mehta, R., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. Simon, TG., Bonilla, H., Yan, P., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature. Kim, MH., Kim, MY., Salloum, S., et al.[2022]

In a study of 1,036 patients with stage I or II hepatocellular carcinoma (HCC), those using statins had a longer median survival of 23.9 months compared to 18.9 months for nonusers, suggesting a potential benefit.

However, after adjusting for various biases and confounding factors, statin use was not significantly associated with improved survival rates, indicating that statins do not enhance survival in elderly patients with early-stage liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin Use and Survival with Early-Stage Hepatocellular Carcinoma. Jeon, CY., Goodman, MT., Cook-Wiens, G., et al.[2017]

In a study of 1,072 patients with nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis, those with bridging fibrosis (F3) showed no cases of hepatocellular carcinoma (HCC) during follow-up, indicating a low risk for this group.

Among patients with cirrhosis (F4), the annual incidence of HCC was 1.90 per 100 person-years, and statin use was associated with a significantly lower risk of developing HCC, with a 23.6% reduction in risk for each additional year of statin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis. Pinyopornpanish, K., Al-Yaman, W., Butler, RS., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemically induced mouse liver tumors are resistant to treatment with atorvastatin. Braeuning, A., Bucher, P., Hofmann, U., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of statins and other lipid-lowering agents. Björnsson, ES.[2022]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property. Hyogo, H., Yamagishi, S., Maeda, S., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Simon, TG., Duberg, AS., Aleman, S., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin use and risk of hepatocellular carcinoma in a U.S. population. McGlynn, KA., Divine, GW., Sahasrabuddhe, VV., et al.[2021]

References

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

Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis. [2019]

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

Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. [2022]

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

Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature. [2022]

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

Statin Use and Survival with Early-Stage Hepatocellular Carcinoma. [2017]

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

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Chemically induced mouse liver tumors are resistant to treatment with atorvastatin. [2022]

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

Hepatotoxicity of statins and other lipid-lowering agents. [2022]

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]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property. [2022]

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

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Statin use and risk of hepatocellular carcinoma in a U.S. population. [2021]