Overall Survival, Tumor Responses
Conditions
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.
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
Interventions
Atorvastatin or placebo will be administered according to randomized allocations.
DRUGPlacebo Oral Tablet
Atorvastatin or placebo will be administered according to randomized allocations.
Sponsors
Taichung Veterans General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | Three year |
Secondary
| Measure | Time frame |
|---|---|
| Best tumor response | Three year |
| Progression free survival | Three year |
Countries
Taiwan
Outcome results
None listed