Statin Combination Therapy in Patients Receiving Sorafenib for Advanced Hepatocellular Carcinoma

Phase 2

Terminated

• Conditions: Overall Survival; Tumor Responses
• Interventions: Drug: Atorvastatin 10mg; Drug: Placebo Oral Tablet

• Registration Number: NCT03275376
• Lead Sponsor: Taichung Veterans General Hospital

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

Study Timeline

• Study First Submitted: 2017-09-05
• Study First Submitted QC: 2017-09-05
• Study First Posted: 2017-09-07
• Study Start: 2017-12-21
• Primary Completion: 2020-12-21
• Status Verified: 2021-03
• Study Completion: 2021-03-13
• Last Update Submitted: 2021-03-14
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin treated group	Atorvastatin 10mg	-
Control group	Placebo Oral Tablet	-

Primary Outcome Measures

Name	Time	Method
Overall survival	Three year

Secondary Outcome Measures

Name	Time	Method
Best tumor response	Three year
Progression free survival	Three year

Trial Locations

Locations (1)

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan