Hepatocellular Carcinoma
Conditions
Brief summary
Metformin is a widely used oral drug for type 2 diabetes and its antitumor effects have got much more attentions recently. It has been shown that metformin exerts anti-cancer activities in several cancers, including primary liver cancer. In this phase II study, safety and efficacy of the combination of metformin and sorafenib will be evaluated in patients with advanced hepatocellular carcinoma.
Detailed description
Sorafenib is the standard choice for advanced hepatocellular carcinoma (BCLC-C), but the efficacy is not satisfied. Metformin is a widely used oral drug for type 2 diabetes and its antitumor effects have got much more attentions recently. It has been shown that metformin exerts anti-cancer activities in several cancers, including primary liver cancer. Recent studies suggest that metformin treatment can reduce the risk of HCC in patients with type 2 diabetes and inhibit HCC invasion and increase drug sensitivity to sorafenib, however, the safety and efficacy of combined therapy for advanced hepatocellular carcinoma remains unclear. In this phase II study, patients with advanced hepatocellular carcinoma, measurable disease, and an Eastern Cooperative Oncology Group performance score≤1 will be enrolled. Eligible subjects will be randomly assigned to receive the treatment of sorafenib or metformin plus sorafenib. The potential improvement of overall survival, time to progression and safety will be evaluated.
Interventions
DRUGSorafenib
Standard treatment for advanced HCC
DRUGMetformin
To evaluate the safety and efficacy of the combined treatment of Metformin and Sorafenib for advanced HCC
Sponsors
First Affiliated Hospital of Harbin Medical University
Harbin Medical University
Liaoning Cancer Hospital & Institute
Shanghai Zhongshan Hospital
Fudan University
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document 2. Confirmed hepatocellular carcinoma according to one of following three criteria: histopathology,Two radiographic techniques (US, MRI, CT, or Angiography) that confirm lesion with typical arterial hypervascularization,Barcelona Clinical Liver Cancer staging C (BCLC-C) 3. Age \> 18 years old 4. Patients with liver disease classified as Child Pugh class A 5. Eastern Clinical Oncology Group (ECOG) performance status 0，1 or 2 (Appendix I) 6. Hemoglobin ≥ 9 g/dL 7. Absolute Neutrophil count（ANC）≥ 1,500 /mm3 8. Platelet count≥ 50,000 /ul 9. Total Bilirubin \< 2 mg/dL 10. Transaminases (SGOT and SGPT) no more than 5 times the upper limit of normal 11. Alkaline phosphatase \< 4 times the upper limit of normal 12. Both men and women and members of all races and ethnic groups are eligible for this study 13. Prothrombin time \> 50% 或 PT-INR \< 2.3
Exclusion criteria
1. Child Pugh Score is 7 with ascites 2. Severe cardiovascular disease 3. Uncontrollable hypertension 4. History of HIV infection 5. Active clinical severe infection（\>grade 2 ，NCI-CTCAE Version3.0） 6. Women who are pregnant 7. Administration of any systemic chemotherapy within the last 6 months 8. Presence of History of gastrointestinal bleeding before randomization 9. Epileptic seizures requiring drug therapy 10. History of allograft transplantation 11. Patients with signs of bleeding or medical history 12. Patients undergoing kidney dialysis 13. Metastatic liver cancer 14. Uncontrollable ascites 15. Encephalopathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | 12 months or time to death |
Secondary
| Measure | Time frame |
|---|---|
| Time To Progression | 12 months or time to death |
| Progression Free Survival | 12 months |
| Objective Response Rate | 12 months |
Countries
China
Contacts
Primary ContactZhao Yan, PhD
Backup ContactDongyan Cheng, MS
Outcome results
None listed