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Metformin Plus Sorafenib for Advanced HCC

Primary Purpose

Hepatocellular Carcinoma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Sorafenib

Metformin

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Tianjin Medical University Cancer Institute and HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sorafenib and Metformin

Sorafenib Alone

Arm Description

Sorafenib 400μg tablet by mouth and Metformin 500mg tablet by mouth with meal, twice per day

Sorafenib 400μg tablet by mouth, twice per day

Outcomes

Primary Outcome Measures

Overall Survival

Secondary Outcome Measures

Time To Progression

Progression Free Survival

Objective Response Rate

Full Information

NCT ID

NCT02672488

First Posted

December 7, 2015

Last Updated

February 2, 2016

Sponsor

Tianjin Medical University Cancer Institute and Hospital

Collaborators

First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Liaoning Tumor Hospital & Institute, Shanghai Zhongshan Hospital, Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT02672488

Brief Title

Metformin Plus Sorafenib for Advanced HCC

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Unknown status

Study Start Date

December 2015 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tianjin Medical University Cancer Institute and Hospital

Collaborators

First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Liaoning Tumor Hospital & Institute, Shanghai Zhongshan Hospital, Fudan University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib and Metformin

Arm Type

Experimental

Arm Description

Sorafenib 400μg tablet by mouth and Metformin 500mg tablet by mouth with meal, twice per day

Arm Title

Sorafenib Alone

Arm Type

Active Comparator

Arm Description

Sorafenib 400μg tablet by mouth, twice per day

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

Nexavar

Intervention Description

Standard treatment for advanced HCC

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Glucophage

Intervention Description

To evaluate the safety and efficacy of the combined treatment of Metformin and Sorafenib for advanced HCC

Primary Outcome Measure Information:

Title

Overall Survival

Time Frame

12 months or time to death

Secondary Outcome Measure Information:

Title

Time To Progression

Time Frame

12 months or time to death

Title

Progression Free Survival

Time Frame

12 months

Title

Objective Response Rate

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhao Yan, PhD

Phone

+862223340123

Ext

6012

chengdongyan916@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Dongyan Cheng, MS

Phone

+862223359984

chengdongyan916@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ti Zhang, MD

Organizational Affiliation

Tianjin Medical University Cancer Institute and Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tianjin Medical University Cancer Institute and Hospital

City

Tianjin

ZIP/Postal Code

300060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

TI ZHANG, MD

Phone

+862223340123

Ext

3092

zhangti@tjmuch.com

First Name & Middle Initial & Last Name & Degree

Huikai Li, MD

Phone

+862223340123

Ext

3091

lihuikai@tjmuch.com

12. IPD Sharing Statement

Plan to Share IPD

Yes

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Metformin Plus Sorafenib for Advanced HCC

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