Safety and Efficacy of Metformin Plus Sorafenib as First-line Therapy in Patients With Advanced Hepatocellular Carcinoma(BCLC-C): A Phase 2 Randomized Study
试验速览
- 阶段
- 2 期
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document
- •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)
- •Age > 18 years old
- •Patients with liver disease classified as Child Pugh class A
- •Eastern Clinical Oncology Group (ECOG) performance status 0，1 or 2 (Appendix I)
- •Hemoglobin ≥ 9 g/dL
- •Absolute Neutrophil count（ANC）≥ 1,500 /mm3
- •Platelet count≥ 50,000 /ul
- •Total Bilirubin < 2 mg/dL
- •Transaminases (SGOT and SGPT) no more than 5 times the upper limit of normal
- •Alkaline phosphatase < 4 times the upper limit of normal
- •Both men and women and members of all races and ethnic groups are eligible for this study
- •Prothrombin time > 50% 或 PT-INR < 2.3
排除标准
- •Child Pugh Score is 7 with ascites
- •Severe cardiovascular disease
- •Uncontrollable hypertension
- •History of HIV infection
- •Active clinical severe infection（>grade 2 ，NCI-CTCAE Version3.0）
- •Women who are pregnant
- •Administration of any systemic chemotherapy within the last 6 months
- •Presence of History of gastrointestinal bleeding before randomization
- •Epileptic seizures requiring drug therapy
- •History of allograft transplantation
- •Patients with signs of bleeding or medical history
- •Patients undergoing kidney dialysis
- •Metastatic liver cancer
- •Uncontrollable ascites
- •Encephalopathy
研究组 & 干预措施
Sorafenib and Metformin
Sorafenib 400μg tablet by mouth and Metformin 500mg tablet by mouth with meal, twice per day
干预措施: Sorafenib (Drug)
Sorafenib and Metformin
Sorafenib 400μg tablet by mouth and Metformin 500mg tablet by mouth with meal, twice per day
干预措施: Metformin (Drug)
Sorafenib Alone
Sorafenib 400μg tablet by mouth, twice per day
干预措施: Sorafenib (Drug)
结局指标
主要结局
Overall Survival
时间窗: 12 months or time to death
次要结局
- Time To Progression(12 months or time to death)
- Progression Free Survival(12 months)
- Objective Response Rate(12 months)