Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence

NCT03219372 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: IIT2017-08-HUSSAIN-STATLV1R01CA218486-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma; Liver Cirrhoses

Outcome Measures

Primary Outcomes (1)

• Time to Recurrence

  Mean difference in time (in months) from baseline (study visit 1) to first hepatocellular cancer (HCC) recurrence or HCC death within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo. \- HCC recurrence will be confirmed by central expert independent radiographic review.

  12 months from baseline

Secondary Outcomes (7)

• Recurrence Free Survival

  12 months from baseline

• Overall Survival

  12 months from baseline

• Waitlist Drop-off

  12 months from baseline

• Change in Liver Stiffness

  12 months from baseline

• Change in Liver Fat Fraction

  12 months from baseline

Study Arms (2)

Pravastatin Pill

EXPERIMENTAL

Daily pravastatin (40mg)

Drug: Pravastatin Pill

Placebo Oral Tablet

PLACEBO COMPARATOR

Placebo

Drug: Placebo Oral Tablet

Interventions

Pravastatin Pill DRUG

statin

Also known as: statin

Pravastatin Pill

Placebo Oral Tablet DRUG

placebo

Also known as: placebo

Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• One lesion ≤ 5 cm or two to three lesions, each ≤ 3 cm.
• One lesion \> 5 cm and ≤ 8 cm.
• 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.
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Pravastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Limitations and Caveats

Accrual fell well below target. One subject was randomized to the study and withdrew prior to completion. Outcome measures were not analyzed due to insufficient accrual.

Results Point of Contact

• Title: Shehnaz K. Hussain, PhD, ScM
• Organization: Cedars Sinai Medical Center

Shehnaz.Hussain@cshs.org

310-429-9859

Study Officials

• Shehnaz Hussain, PhD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 1:1 drug versus placebo

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 17, 2017
• Study Start: September 27, 2018
• Primary Completion: December 4, 2018
• Study Completion: March 5, 2019
• Last Updated: January 22, 2021
• Results First Posted: January 22, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)