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Trial record 1 of 1 for:    NCT03219372
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Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence

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ClinicalTrials.gov Identifier: NCT03219372
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : June 19, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Shehnaz Hussain, Cedars-Sinai Medical Center

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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Cirrhoses Drug: Pravastatin Pill Drug: Placebo Oral Tablet Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1 drug versus placebo
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double-blind
Primary Purpose: Prevention
Official Title: Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pravastatin Pill
Daily pravastatin (40mg)
Drug: Pravastatin Pill
statin
Other Name: statin

Placebo Comparator: Placebo Oral Tablet
Placebo
Drug: Placebo Oral Tablet
placebo
Other Name: placebo




Primary Outcome Measures :
  1. Time to Recurrence [ Time Frame: 12 months from baseline ]

    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.



Secondary Outcome Measures :
  1. Recurrence Free Survival [ Time Frame: 12 months from baseline ]

    Mean difference in time (in months) from baseline (study visit 1) to first occurrence of a documented hepatocellular cancer (HCC) recurrence 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.


  2. Overall Survival [ Time Frame: 12 months from baseline ]
    Mean difference in time (in months) from baseline (study visit 1) to death (for any reason) within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

  3. Waitlist drop-off [ Time Frame: 12 months from baseline ]
    Mean difference in time from baseline (study visit 1) to liver transplant waitlist drop-off within 12 months following treatment initiation for subjects randomized to pravastatin versus subjects randomized to placebo.

  4. Change in liver stiffness [ Time Frame: 12 months from baseline ]
    Mean difference in mean change in liver stiffness (as measured by MRE or FibroScan) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

  5. Change in liver fat fraction [ Time Frame: 12 months from baseline ]
    Mean difference in within-person change in liver fat fraction (as measured by MRE) between baseline (study visit 1) and 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.

  6. Change in Inflammatory Biomarkers [ Time Frame: 12 months from baseline ]
    Mean difference in biomarkers (eg. IL6, TNFα, sTNFRII, IL18BP, sCD163, IL10, IL17, IL-8, CCL17, TGFβ, β-catenin, glutamine synthetase) from baseline (study visit 1) to 12 months (study visit 6) for subjects randomized to pravastatin versus subjects randomized to placebo.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

    • a. One lesion ≤ 5 cm or two to three lesions ≤ 3 cm.
    • b. One lesion > 5 cm and ≤ 8 cm.
    • c. Two or three lesions each > 3 cm and ≤ 5 cm, and a total diameter of all lesions ≤ 8 cm.
    • d. Four or five lesions each < 3 cm, and a total diameter of all lesions ≤ 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219372


Contacts
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Contact: Sandra Conteras 424-315-2216 Sandra.Contreras@cshs.org
Contact: Shehnaz Hussain, PhD 310-423-6401 Shehnaz.Hussain@cshs.org

Locations
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United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Shehnaz Hussain, PhD    310-423-6401    Shehnaz.Hussain@cshs.org   
Contact: Sandra Contreras    424-315-2216    sandra.contreras@cshs.org   
Sub-Investigator: Walid S Ayoub, MD         
Sub-Investigator: Marc T Goodman, PhD         
Sub-Investigator: Mazen Noureddin, MD         
Sub-Investigator: Laura M Kulik, MD         
Sub-Investigator: Vatche Agopian, MD         
Sub-Investigator: Richard Finn, MD         
Sub-Investigator: David Lu, MD         
Sub-Investigator: Otoniel Martinez-Maza, PhD         
Sub-Investigator: Saeed Sadeghi, MD         
Sub-Investigator: Vinay Sundaram, MD         
Sub-Investigator: Marc L Friedman, MD         
Sub-Investigator: H G Lipshutz, MD         
Sub-Investigator: Jonathan Steinberger, MD         
Sub-Investigator: Ju Dong Yang, MD         
Sponsors and Collaborators
Cedars-Sinai Medical Center
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Shehnaz Hussain, PhD Cedars-Sinai Medical Center

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Responsible Party: Shehnaz Hussain, Associate Professor, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT03219372     History of Changes
Other Study ID Numbers: IIT2017-08-HUSSAIN-STATLV
1R01CA218486-01 ( U.S. NIH Grant/Contract )
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Liver Cirrhosis
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pathologic Processes
Disease Attributes
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors