Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Overall Survival, Tumor Responses

Intervention / Treatment
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* Drug: Atorvastatin 10mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Statin treated group<br> | Drug: Atorvastatin 10mg<br>* Atorvastatin or placebo will be administered according to randomized allocations.<br>|
| Placebo Comparator: Control group<br> | Drug: Placebo Oral Tablet<br>* Atorvastatin or placebo will be administered according to randomized allocations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Three year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best tumor response |  | Three year | 
| Progression free survival |  | Three year |