Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma

March 14, 2021 updated by: Teng-Yu Lee, Taichung Veterans General Hospital

Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma: A Randomized Controlled Study

Target therapy with sorafenib is the standard of treatment for advanced Hepatocellular carcinoma (HCC), but the patient survival time is still unsatisfactory. The aims of this study are to prove statins improve the tumor responses and overall survival for patients who receive sorafenib therapy for advanced HCC by a prospective randomized controlled study.

Study Overview

Detailed Description

Background:

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, including the condition in Taiwan, and the management of HCC is an important challenge in public health. Target therapy with sorafenib is the standard of treatment for advanced HCC (vascular invasion or extrahepatic metastasis), but the patient survival time is still unsatisfactory. In recent years, growing evidences, including mechanism analysis, have suggested the anitneoplastic effects of statin, and a recent pooled analysis found that statin use may be associated with improved survival in patients with metastatic rencal cell carcinoma. However, a prospective clinical trial of statin sorafenib combination therapy in the treatment of advanced HCC is lacking.

Aims:

  1. To prove statins improve the overall survival for patients who receive sorafenib therapy for advanced HCC by a prospective randomized controlled study.
  2. To prove statin can improve tumor responses and the progression free survival for patients who receive sorafenib therapy for advanced HCC by a prospective randomized controlled study.

Methods:

This randomized placebo-controlled study will prospectively enroll patients who receiving sorafenib therapy for advanced HCC in the Taichung Veterans General Hospital, and statin or placebo will be statin or placebo will be administered according to randomized allocations. Tumor responses, time to tumor progression, and survival time will be followed and recorded

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients more than 40 years old
  2. HCCs diagnosed by AASLD image criteria or pathology
  3. HCCs in BCLC advanced stage, with portal vein thrombosis (VP3 or VP4) or extrahepatic metastasis
  4. Not suitable or failed to locoreginal treatments for HCC
  5. Child-Pugh score = or < 6
  6. ECOG performance status (PST) 0-2
  7. Serum bilirubin < 2 mg/dL and prothrombin time (PT) prolongation < 3 seconds
  8. Will receive sorafenib therapy
  9. Life expectancy > 3 months
  10. Will follow the pregnancy prevention protocol

Exclusion Criteria:

  1. HCC is considered for curative therapy
  2. HCC with brain metastasis
  3. History of systemic therapy for HCC
  4. Indications for statin use, such as hyperlipidemia in cardiovascular diseases
  5. Any local treatment for HCC within 4 weeks
  6. Any active gastrointestinal bleeding within 4 weeks
  7. Liver transplant history or concomitant immunosuppressive therapy
  8. Concurrent any other malignancy
  9. Allergy to sorafenib or statins
  10. Pregnancy or lactation
  11. Serum AST or ALT > 5x upper limit of normal
  12. Known HIV infection
  13. eGFR < 30 ml/min
  14. Abnormal medical conditions that are unsuitable for study, such as uncontrolled hypertension, coronary arterial disease, or arrhythmia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control group
Atorvastatin or placebo will be administered according to randomized allocations.
Experimental: Statin treated group
Atorvastatin or placebo will be administered according to randomized allocations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: Three year
Three year

Secondary Outcome Measures

Outcome Measure
Time Frame
Best tumor response
Time Frame: Three year
Three year
Progression free survival
Time Frame: Three year
Three year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Teng-Yu Lee, MD, Taichung Veterans General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 1. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-390. 2. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34. 3. Cainap C, Qin S, Huang WT, et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015;33:172-179. 4. Llovet JM, Decaens T, Raoul JL, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 2013;31:3509-3516. 5. Singh S, Singh PP, Roberts LR, et al. Chemopreventive strategies in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2014;11:45-54. 6. Demierre MF, Higgins PD, Gruber SB, et al. Statins and cancer prevention. Nat Rev Cancer 2005;5:930-942. 7. Wu J, Wong WW, Khosravi F, et al. Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis. Cancer Res 2004;64:6461-6468. 8. Rao S, Porter DC, Chen X, et al. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc Natl Acad Sci U S A 1999;96:7797-7802. 9. El-Serag HB, Johnson ML, Hachem C, et al. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology 2009;136:1601-1608. 10. Tsan YT, Lee CH, Wang JD, et al. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol 2012;30:623-630. 11. Chiu HF, Ho SC, Chen CC, et al. Statin use and the risk of liver cancer: a population-based case-control study. Am J Gastroenterol 2011;106:894-898.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2017

Primary Completion (Actual)

December 21, 2020

Study Completion (Actual)

March 13, 2021

Study Registration Dates

First Submitted

September 5, 2017

First Submitted That Met QC Criteria

September 5, 2017

First Posted (Actual)

September 7, 2017

Study Record Updates

Last Update Posted (Actual)

March 16, 2021

Last Update Submitted That Met QC Criteria

March 14, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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