- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03275376
Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma
Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma: A Randomized Controlled Study
Study Overview
Status
Conditions
Intervention / Treatment
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:
- To prove statins improve the overall survival for patients who receive sorafenib therapy for advanced HCC by a prospective randomized controlled study.
- 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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Taichung, Taiwan, 40705
- Taichung Veterans General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
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
Investigators
- Principal Investigator: Teng-Yu Lee, MD, Taichung Veterans General Hospital
Publications and helpful links
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
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma, Hepatocellular
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
Other Study ID Numbers
- CF16263B
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Overall Survival
-
Peking University First HospitalCompletedOverall SurvivalChina
-
Guangdong Association of Clinical TrialsUnknown
-
Peking University First HospitalPeking University Third Hospital; Beijing HospitalRecruitingSurgery | Elderly | Dexmedetomidine | Intensive Care Unit | Overall SurvivalChina
-
Shanghai Minimally Invasive Surgery CenterUnknownPostoperative Complications | Overall SurvivalChina
-
Hospital Universitario Virgen de la ArrixacaCompletedRecurrence | Overall Survival | Disease-free SurvivalSpain
-
Peking Union Medical College HospitalOrigiMedRecruitingQuality of Life | Objective Response Rate | Overall Survival | Progression-free Survival | Disease Control Rate | Duration of Response | Five-year Survival RateChina
-
Qingdao Central HospitalCompletedOverall SurvivalChina
-
Shanghai CP Guojian Pharmaceutical Co., Ltd.CompletedAdverse Events | Progress-free Survival | Overall Response Rate
-
Qingdao Central HospitalRecruiting
-
Peking University People's HospitalXijing Hospital; Peking Union Medical College Hospital; Chinese PLA General Hospital and other collaboratorsWithdrawnToxicity | Overall Survival | Progression-free SurvivalChina
Clinical Trials on Atorvastatin 10mg
-
Organon and CoCompleted
-
GlaxoSmithKlineCompletedDiabetes Mellitus, Type 2Korea, Republic of, Malaysia, Philippines, Thailand, Russian Federation, Mexico
-
Daewon Pharmaceutical Co., Ltd.CompletedHypercholesterolemia, DyslipidemiaKorea, Republic of
-
Zhejiang Hisun Pharmaceutical Co. Ltd.Unknown
-
Samsung Medical CenterNot yet recruiting
-
Yooyoung Pharmaceutical Co., Ltd.CompletedCombined DyslipidemiaKorea, Republic of
-
GlaxoSmithKlineCompletedDyslipidemias | DyslipidaemiasUnited States
-
Sang Hak LeeUnknownMixed HyperlipidemiaKorea, Republic of
-
National Cardiovascular Center Harapan Kita Hospital...CompletedMyocardial Edema
-
Prof. Stephen LeePfizer; Queen Mary Hospital, Hong KongCompletedCoronary Disease | Hydroxymethylglutaryl-CoA Reductase Inhibitors | Ultrasonography, InterventionalChina