Metformin Plus Sorafenib for Advanced HCC

• ClinicalTrials.gov Identifier: NCT02672488
• Recruitment Status: Unknown
• First Posted: February 3, 2016
• Last Update Posted: February 3, 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
• Information provided by (Responsible Party): Tianjin Medical University Cancer Institute and Hospital

Tracking Information

• First Submitted Date: December 7, 2015
• First Posted Date: February 3, 2016
• Last Update Posted Date: February 3, 2016
• Study Start Date: December 2015
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 2, 2016): Overall Survival [ Time Frame: 12 months or time to death ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 2, 2016)

• Time To Progression [ Time Frame: 12 months or time to death ]
• Progression Free Survival [ Time Frame: 12 months ]
• Objective Response Rate [ Time Frame: 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

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

Study Arms

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

  • Drug: Sorafenib
  • Drug: Metformin
• Active Comparator: Sorafenib Alone
  Sorafenib 400μg tablet by mouth, twice per day
  Intervention: Drug: Sorafenib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: February 2, 2016): 82
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02672488
• Other Study ID Numbers: METSOR
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Tianjin Medical University Cancer Institute and Hospital
• Study 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

Investigators

• Principal Investigator: Ti Zhang, MD; Tianjin Medical University Cancer Institute and Hospital

• PRS Account: Tianjin Medical University Cancer Institute and Hospital
• Verification Date: December 2015