Efficacy and Safety of Sorafenib (Nexavar) in Combination With Gemcitabine in Advanced Hepatocellular Carcinoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00703365
Recruitment Status : Completed
First Posted : June 23, 2008
Last Update Posted : August 29, 2011
Chulalongkorn University
Bumrungrad International Hospital
Information provided by (Responsible Party):
Mahidol University

Brief Summary:
This study is to evaluate the efficacy and safety of Sorafenib in combination with Gemcitabine in patients with advanced/unresectable HCC.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Sorafenib and Gemcitabine Phase 2

Detailed Description:

Hepatocellular carcinoma (HCC), also known as primary liver cancer, is the fifth most common cancer in the world. It is responsible for about 90 percent of the primary malignant liver tumors observed in adult and disproportionately affects men, with about three times as many men developing the disease as women.

Common symptoms in patients affected with HCC include abdominal pain, weight loss, weakness, fullness and anorexia, abdominal swelling, jaundice and vomiting.

Multiple clinical staging systems for hepatic tumors have been used such as the American Joint Committee on Cancer TNM system (stage 0, A, B, C, D) etc. However, the staging systems are still evolving with all attempts to improve the classification and prognosis prediction of HCC, and there is no agreement on the best staging that can be recommended world-wide.

For advanced HCC, sorafenib is likely to become the new standard of care. Combinational therapies with sorafenib have the potential to further improved therapeutic options for patients suffering from advanced HCC. Gemcitabine is a classical chemotherapeutic substance that has modest anti-cancer activity in HCC. However, its anti-cancer activity seems to be improved when combined with other anti-cancer drugs including drugs interfering with the VEGF pathway. Both substances, sorafenib and gemcitabine, have a favorable safety profile with a minimal overlap of side effects. Further the mode of actions of sorafenib and gemcitabine are likely to result in synergistic anti-tumor effects.

An open label, single arm, multicenter phase II study designed to determine progression free survival of patients with advanced stage HCC treated with sorafenib in combination with gemcitabine. Patients will receive up to 6 cycles of gemcitabine(IV 1000 mg/m2 on day 1, 8, 15 of a 28-day cycle) in combination with sorafenib (400 mg po bid daily) followed by sorafenib (400 mg po bid daily) maintenance until disease progression.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label, Single Arm, Phase II Study to Investigate the Efficacy and Safety of Sorafenib (Nexavar) in Combination With Gemcitabine in Patients With Advanced Hepatocellular Carcinoma (HCC)
Study Start Date : February 2008
Actual Primary Completion Date : January 2010
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Drug: Sorafenib and Gemcitabine
Sorafenib 400 mg po bid daily and Gemcitabine IV 1,000 mg/m2 on day 1,8, 15 of a 28-day cycle (up to 6 cycles), then followed by Sorafenib 400 mg po bid daily maintenance until disease progression.
Other Name: Nexavar and Gemzar

Primary Outcome Measures :
  1. To evaluate the efficacy (progression free survival (PFS)) of sorafenib in patients with advanced/unresectable HCC. [ Time Frame: 2.5 years ]

Secondary Outcome Measures :
  1. To evaluate overall, survival, overall response rate (RECIST), time to progression (TTP), disease control rate (DCR) and side-effect profile of sorafenib in combination with gemcitabine in patients suffering from HCC. [ Time Frame: 2.5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • patient at least 18 years of age with written informed consent prior to enrollment into the study.
  • histologically or cytologically confirmed advanced unresectable and/or metastasis) HCC
  • Child-Pugh class A or B
  • Have measurable disease according to RECIST criteria
  • life expectancy of at least 12 weeks, ECOG 0-2
  • Have adequate bone marrow reserve and liver and renal function at screening
  • Practice adequate contraception during study participation

Exclusion Criteria:

  • Exclude medical conditions including history of cardiac disease, HIV infection,active infection,brain metastastasis or intracranial metastasis,seizure disorder requiring medication, history of organ allograft,evidence of or history of bleeding diathesis,previous or concurrent cancer with distinct in primary site or histology (with exception of cervical carcinoma in situ and treated basal cell carcinoma
  • Excluded therapies and medications, previous and concomitant : prior systemic anticancer chemotherapy or immunotherapy or targeted therapy,hormonal therapy within 2 weeks,local treatment modality within 4 weeks,radiotherapy within 3 weeks,major surgery and unhealed wound within 4 weeks,autologous bone marrow transplant or stem cell rescue within 4 months
  • other condition that may interfere with the patient's participation in the study or evaluation of the results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00703365

Department of Medicine, Siriraj Hospital
Bangkoknoi, Bangkok, Thailand, 10700
Medical Oncology Unit, Chulalongkorn Hospital
Patumwan, Bangkok, Thailand, 10330
Horizon Regional Cancer Center, Bamrungrad Hospital
Sukhumvit 3, Bangkok, Thailand, 10110
Sponsors and Collaborators
Mahidol University
Chulalongkorn University
Bumrungrad International Hospital
Principal Investigator: Vichien Srimuninnimit, Assist.Prof. Siriraj Hospital, Bangkok, Thailand

Responsible Party: Mahidol University Identifier: NCT00703365     History of Changes
Other Study ID Numbers: 12849
First Posted: June 23, 2008    Key Record Dates
Last Update Posted: August 29, 2011
Last Verified: August 2011

Keywords provided by Mahidol University:
Hepatocellular Carcinoma (HCC)

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vitamin B Complex
Growth Substances