Metformin Plus Sorafenib for Advanced HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

Safety and Efficacy of Metformin Plus Sorafenib as First-line Therapy in Patients With Advanced Hepatocellular Carcinoma(BCLC-C): A Phase 2 Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02672488
• Other study ID #: METSOR
• Status: Recruiting
• Phase: Phase 2
• First received: December 7, 2015
• Last updated: February 2, 2016
• Start date: December 2015
• Est. completion date: December 2018

Study information

• Verified date: December 2015
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: Zhao Yan, PhD
• Phone: +862223340123
• Email: chengdongyan916[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 82
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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% ? 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Sorafenib
Standard treatment for advanced HCC
• Metformin
To evaluate the safety and efficacy of the combined treatment of Metformin and Sorafenib for advanced HCC

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin

Sponsors (6)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital	First Affiliated Hospital of Harbin Medical University, Fudan University, Harbin Medical University, Liaoning Tumor Hospital & Institute, Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		12 months or time to death	No
Secondary	Time To Progression		12 months or time to death	No
Secondary	Progression Free Survival		12 months	No
Secondary	Objective Response Rate		12 months	No