Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence

To date, there has been a scarcity of clinical trials evaluating the effectiveness of
adjuvant therapies in patients with early stage HCC, although it is widely considered an area
of highly unmet need.

The objective of this randomized double-blinded, placebo-controlled Phase II trial is to
examine the effects of pravastatin use versus placebo after 12 months of treatment on
hepatocellular cancer (HCC) recurrence in 130 patients with liver cirrhosis, HCC meeting
Milan Criteria for tumor burden, and initial locoregional therapy (LRT) with adequate
response.

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 the Milan criteria prior to LRT. Criteria fulfillment
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.

- 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

- 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)