Pravastatin Sodium in Preventing Liver Cancer Recurrence
This randomized phase II trial studies how well pravastatin sodium works in preventing liver cancer from coming back (recurrence). Pravastatin sodium in combination with therapies targeting the liver may delay or protect against liver cancer from occurring again.
Inclusion Criteria
- Confirmed diagnosis of liver cirrhosis (Child-Pugh A or B) assessed by the presence of clinical signs, symptoms, body imaging, or liver biopsy
- Diagnosis of HCC falling within one of the following criteria prior to locoregional therapy (LRT) * One lesion =< 5 cm or two to three lesions, each =< 3 cm * One lesion > 5 cm and =< 8 cm * Two or three lesions, of with at least one is > 3 cm and all are =< 5 cm each; the sum of all diameters must be =< 8 cm * Four or five lesions, each < 3 cm; the sum of all diameters must be =< 8 cm Criteria fulfillment will be confirmed by the Imaging Charter and MedQIA
- Initiation of LRT (according to clinical judgement) within 24 months prior to screening visit, with adequate response as determined by Imaging Charter and MedQIA
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal (ULN)
- Alpha-fetoprotein (AFP) < 400 ng/mL
- Ability to understand and the willingness to sign a written informed consent document and medical release
- Agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; for women who are able to become pregnant
- Willing and able to comply with trial protocol and follow-up
Exclusion Criteria
- Current use of statin medication or statin use within 12 months of screening visit
- Current systemic use of medications known to interact with statins and potentially increase toxicity, including (e.g., gemfibrozil, cyclosporine, clarithromycin, colchicine, niacin and fibrates)
- History of adverse effects, intolerance, or allergic reactions attributed to compounds of similar chemical or biologic composition to pravastatin (i.e., other statin medications)
- Current use of any other investigational agents
- Women who are pregnant; women who are able to become pregnant must have a confirmed negative pregnancy test prior to enrollment
- Women who are breastfeeding; it is not known whether pravastatin 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 pravastatin, breastfeeding should be discontinued if the mother is treated with pravastatin
- Prior liver transplant
- Model for End-Stage Liver Disease (MELD) score >= 30
- History of chronic myopathy
- Active malignancy within the past 5 years (excluding HCC, basal/squamous cell skin cancer, or prostate cancer with a Gleason score 6 or less)
- Known human immunodeficiency virus (HIV) infection
- Hemophilia
- Concurrent illness which in the opinion of the investigators would compromise either the patient or the integrity of the data
- Concurrent excessive alcohol consumption (average alcohol consumption of more than 5 drinks per day)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03219372.
PRIMARY OBJECTIVE:
I. To evaluate the effect of a pravastatin sodium (pravastatin) intervention versus placebo on the change in time to recurrence (TTR) from baseline to 12 months following treatment initiation.
SECONDARY OBJECTIVES:
I. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on recurrence free survival.
II. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on overall survival.
III. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on waitlist drop-off.
IV. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on change in liver stiffness.
V. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on change in liver fat fraction.
VI. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on change in serum biomarkers of monocyte/macrophage and stellate cell activation.
VII. To evaluate the effect of a pravastatin intervention versus placebo at 12 months from baseline on levels of liver tissue markers related to hepatocellular carcinoma (HCC).
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive pravastatin sodium orally (PO) once daily (QD). Treatment continues up to 12 months in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive placebo PO QD. Treatment continues up to 12 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.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationCedars Sinai Medical Center
Principal InvestigatorShehnaz Hussain
- Primary IDIIT2017-08-Hussain-StatLv
- Secondary IDsNCI-2017-01563
- ClinicalTrials.gov IDNCT03219372