CirrhosisPhase 2NCT02968810
Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis
A Phase 2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging in people with Cirrhosis and Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Hepatocellular Carcinoma
- What is being tested?
- Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 21 Jun 2017to 7 Jul 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- Prior known or suspected hepatocellular carcinoma
- Prior cholangiocarcinoma
- Model for end-stage liver disease (MELD) > 20
- Any lab results that do not meet inclusion criteria after the Screen 1 blood tests
- 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)
- Concurrent illness which in the opinion of the investigators would compromise either the patient or the integrity of the data
- Current excessive alcohol consumption (average alcohol consumption of more than 5 drinks per day)
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
Northwestern University
Chicago, Illinois, 60611
Cedars-Sinai Medical Center
Los Angeles, California, 90048
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Puerto Rico2 sites
Centro Comprensivo de Cancer de UPR
San Juan, 00927
University of Puerto Rico
San Juan, 00936
About this study
Official title: Statin Therapy to Reduce Disease Progression From Liver Cirrhosis to Cancer
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the effect of a simvastatin intervention versus placebo on the change in serum AFP-L3% from baseline to 6 months following treatment initiation in patients with liver cirrhosis who have a current model for end-stage liver disease (MELD) =< 20.
SECONDARY OBJECTIVES:
- To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline on the change in:
Ia. Serum AFP; Ib. Serum IL-6; Ic. Serum deoxycholic acid; Id. Liver stiffness; Ie. Fibrosis 4 index (FIB-4) score; If. MELD score.
EXPLORATORY OBJECTIVES:
- To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline on the change in other:
Ia. serum bile acid levels; Ib. serum immune markers.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive simvastatin orally (PO) once daily (QD). Patients also undergo collection of blood on study and computed tomography (CT) scans/magnetic resonance imaging (MRI) throughout the trial.
GROUP II: Patients receive placebo PO QD. Patients also undergo collection of blood on study and CT/MRI throughout the trial.
In both groups, treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30, 60, and 90 days.
- Conditions
- Cirrhosis, Hepatocellular Carcinoma
- Being tested
- Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Placebo Administration, Questionnaire Administration
- Medical subject headings
- Fibrosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Placebo AdministrationOther
Given PO
Questionnaire AdministrationOther
Ancillary studies
SimvastatinDrug
Also called MK 733, Synvinolin, Zocor
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Placebo Administration; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: Baseline to 6 months
Secondary outcomes (6)
Change in Serum AFP
Assessed by liquid-phase binding assay. Mean difference in AFP, a glycoform produced by malignant liver cells.
Measured: Baseline to 6 months
Change in Serum IL-6
Mean difference in IL-6 (interleukin-6) NPX (normalized protein expression).
Measured: Baseline to 6 months
Change in Serum Deoxycholic Acid
Assessed by liquid chromatography coupled with mass spectrometry. Median difference in serum DCA (deoxycholic acid), a secondary bile acid.
Measured: Baseline to 6 months
Change in Liver Stiffness
Assessed by liver elastography. Fibroscan score from a fibroscan examination (a non-invasive measurement of liver fibrosis). A test result of greater than 20kPa is generally associated with an increased HCC risk. Mean difference in liver stiffness.
Measured: Baseline to 6 months
Change in Fibrosis 4 Index Score
The Fib-4 index is a non-invasive measure of liver stiffness. A high score (FIB4 ≥ 3.25) and low score is (FIB4 < 1.3) The FIB-4 index is calculated as follows: FIB-4 = (Age × AST (U/L)) ÷ (PLT (109/L) × (√ ALT (U/L)). Change in mean difference.
Measured: Baseline to 6 months
Change in Model for End-Stage Liver Disease Score
The Model for End-Stage Liver Disease (MELD) is a validated predictor of survival among different populations of patients with advanced liver disease. MELD = 9.57 x ln(creatinine [mg/dL]) + 3.78 x ln(total bilirubin [mg/dL]) + 11.2 x ln(INR) + 6.43. Scores range from 6 (low/ less liver disease) to 40 (high/severe liver disease). Change in mean difference.
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2016 (estimated)
- Study start21 Jun 2017
- Primary completion3 May 2023
- Study completion7 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marc T Goodman, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02968810
- Sponsor's protocol ID
- NCI-2016-01719
- Other IDs
- NCI-2016-01719, N01-CN-2012-00035, NCI2015-06-03, NWU2015-06-03, N01CN00035, P30CA060553
- Status last verified
- Aug 2026
- First submitted
- 18 Nov 2016
- Last updated
- 9 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No