Metformin Plus Sorafenib for Advanced HCC

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sorafenib; Drug: Metformin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300060
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: TI ZHANG, MD; Phone Number: 3092 +862223340123; Email: zhangti@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib and Metformin; Sorafenib 400μg tablet by mouth and Metformin 500mg tablet by mouth with meal, twice per day	Drug: Sorafenib; Standard treatment for advanced HCC; Other Names: Nexavar; Drug: Metformin; To evaluate the safety and efficacy of the combined treatment of Metformin and Sorafenib for advanced HCC; Other Names: Glucophage
Active Comparator: Sorafenib Alone; Sorafenib 400μg tablet by mouth, twice per day	Drug: Sorafenib; Standard treatment for advanced HCC; Other Names: Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	12 months or time to death

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	12 months
Time To Progression	12 months or time to death
Objective Response Rate	12 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Fudan University; Shanghai Zhongshan Hospital; Harbin Medical University; Liaoning Tumor Hospital & Institute; First Affiliated Hospital of Harbin Medical University
• Investigators: Principal Investigator: Ti Zhang, MD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: December 7, 2015
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Estimate): February 3, 2016
• Last Update Submitted That Met QC Criteria: February 2, 2016
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib; Metformin
• Other Study ID Numbers: METSOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes