NCT03275376

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2017

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 5, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 7, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

December 21, 2017

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 21, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2021

Completed
Last Updated

March 16, 2021

Status Verified

March 1, 2021

Enrollment Period

3 years

First QC Date

September 5, 2017

Last Update Submit

March 14, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    Three year

Secondary Outcomes (2)

  • Best tumor response

    Three year

  • Progression free survival

    Three year

Study Arms (2)

Statin treated group

EXPERIMENTAL
Drug: Atorvastatin 10mg

Control group

PLACEBO COMPARATOR
Drug: Placebo Oral Tablet

Interventions

Atorvastatin or placebo will be administered according to randomized allocations.

Statin treated group

Atorvastatin or placebo will be administered according to randomized allocations.

Control group

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Related Publications (1)

  • 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.

    BACKGROUND

MeSH Terms

Interventions

Atorvastatin

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Study Officials

  • Teng-Yu Lee, MD

    Taichung Veterans General Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

September 5, 2017

First Posted

September 7, 2017

Study Start

December 21, 2017

Primary Completion

December 21, 2020

Study Completion

March 13, 2021

Last Updated

March 16, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will not share

Locations