Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence
Condition: Hepatocellular Carcinoma; Liver Cirrhoses
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis; Recurrence
Intervention: Pravastatin Pill; Placebo Oral Tablet
Intervention description: statin; placebo
Intervention MeSH terms: Pravastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 1:1 drug versus placebo
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: double-blind
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly
      among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will
      survive 5 years or more. While locoregional therapies are utilized in an effort to combat
      this disease, the recurrence rate of HCC after these therapies are high.

      Statins are widely used drugs that lower cholesterol levels. Some studies have suggested that
      statins lower risk of HCC recurrence, but this possibility has not been studied thoroughly in
      a clinical trial. This study will examine the effects of pravastatin, a type of statin, on
      time to HCC recurrence in patients with early stage HCC. It is possible that pravastatin in
      combination with locoregional therapies may delay or protect against HCC recurrence.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years

          -  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 LRT. Criteria
             fulfillment will be confirmed by the Imaging Charter and MedQIA.

               1. One lesion ≤ 5 cm or two to three lesions, each ≤ 3 cm.

               2. One lesion > 5 cm and ≤ 8 cm.

               3. Two or three lesions, of which at least one is > 3 cm and all are ≤ 5 cm each.
                  The sum of all diameters must be ≤ 8 cm.

               4. Four or five lesions, each < 3 cm. The sum of all diameters must be ≤ 8 cm.

          -  Initiation of LRT (according to clinical judgement) within 24 months prior to
             Screening Visit, with adequate response as determined by Imaging Charter and MedQIA.

          -  ECOG performance status ≤1 (Karnofsky ≥70%; see Appendix A)

          -  AST (SGOT) & ALT (SGPT) ≤5 × institutional ULN

          -  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

          -  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 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)