Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence

NCT ID: NCT03219372

Last Updated: 2021-01-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-27
• Study Completion Date: 2019-03-05

Brief 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.

Detailed Description

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 or OPTN tumor downstaging criteria for tumor burden, and initial locoregional therapy (LRT) with adequate response.

Conditions

Hepatocellular Carcinoma; Liver Cirrhoses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Pravastatin Pill

Daily pravastatin (40mg)

Group Type: EXPERIMENTAL

Pravastatin Pill

Intervention Type: DRUG

statin

Placebo Oral Tablet

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

placebo

Interventions

Pravastatin Pill

statin

Intervention Type: DRUG

Placebo Oral Tablet

placebo

Intervention Type: DRUG

Other Intervention Names

statin; placebo

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Shehnaz Hussain

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shehnaz Hussain, PhD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01CA218486-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IIT2017-08-HUSSAIN-STATLV

Identifier Type: -

Identifier Source: org_study_id