Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis

NCT02968810 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 6 other identifiers: NCI-2016-01719N01-CN-2012-00035NCI2015-06-03NWU2015-06-03N01CN00035P30CA060553
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 5

Brief Summary

This phase II trial studies how well simvastatin works in preventing liver cancer in patients with liver cirrhosis. Simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Hepatocellular Carcinoma; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Change in Serum AFP-L3%

  Assessed by liquid-phase binding assay. Mean AFP-L3% difference calculated including all participants imputing undetectable values with 0.5%

  Baseline to 6 months

Secondary Outcomes (6)

• Change in Serum AFP

  Baseline to 6 months

• Change in Serum IL-6

  Baseline to 6 months

• Change in Serum Deoxycholic Acid

  Baseline to 6 months

• Change in Liver Stiffness

  Baseline to 6 months

• Change in Fibrosis 4 Index Score

  Baseline to 6 months

Study Arms (2)

Group I (simvastatin)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Simvastatin

Group II (placebo)

PLACEBO COMPARATOR

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Placebo Administration; Other: Questionnaire Administration

Interventions

Questionnaire Administration OTHER

Ancillary studies

Group I (simvastatin); Group II (placebo)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Group I (simvastatin); Group II (placebo)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Group I (simvastatin); Group II (placebo)

Placebo Administration OTHER

Given PO

Group II (placebo)

Simvastatin DRUG

Given PO

Also known as: MK 733, Synvinolin, Zocor

Group I (simvastatin)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Group I (simvastatin); Group II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of liver cirrhosis assessed by the presence of clinical signs, symptoms, body imaging (ultrasound, computed tomography \[CT\], or magnetic resonance imaging \[MRI\]), or liver biopsy
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Leukocytes \>= 2,500/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Platelets \>= 50,000/microliter
• Hemoglobin \>= 8 g/dL
• Total bilirubin =\< 3 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN
• Creatinine =\< 1.5 x institutional ULN
• Women who are able to become pregnant must have a confirmed negative pregnancy test result prior to enrollment; women \>= 50 years of age who have not had a menstrual period in the past year; and women who have had a hysterectomy, both ovaries removed, or a tubal ligation; will not be required to have a pregnancy test
• The effects of simvastatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women who are able to become pregnant must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Ability to understand and the willingness to sign a written informed consent document and medical release
• Willing and able to comply with trial protocol and follow-up
• Have had an abdominal imaging test (CT, MRI, or ultrasound) within the past 18 months

You may not qualify if:

• Prior or current use of statin medication
• Current systemic use of medications known to interact with statins and potentially increase toxicity, including gemfibrozil, cyclosporine, danazol, lomitapide, verapamil, diltiazem, dronedarone, amiodarone, amlodipine, ranolazine, strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, human immunodeficiency virus \[HIV\] protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, or cobicistat-containing products), or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, modafinil, nafcillin)
• History of adverse effects, intolerance, or allergic reactions attributed to compounds of similar chemical or biologic composition to simvastatin (i.e., other statin medications)
• Current use of any other investigational agents
• 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
• Prior liver transplant
• Prior known or suspected hepatocellular carcinoma
• Prior cholangiocarcinoma
• Model for end-stage liver disease (MELD) \> 20
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of chronic myopathy
• Prior germ cell cancer
• History of active malignancy within the past 5 years (excluding basal/squamous cell skin cancer or prostate cancer with a Gleason score 6 or less)
• Known active infection with HIV
• Medical contraindications to blood draw (e.g., hemophilia)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Centro Comprensivo de Cancer de UPR

San Juan, 00927, Puerto Rico

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Fibrosis; Carcinoma, Hepatocellular

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Simvastatin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Seema A. Khan
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Marc T Goodman

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 21, 2016
• Study Start: June 21, 2017
• Primary Completion: May 3, 2023
• Study Completion (Estimated): December 23, 2026
• Last Updated: May 4, 2026
• Results First Posted: April 15, 2025

Record last verified: 2025-12

Locations

US (3); PR (2)