Efficacy and Safety of Sorafenib (Nexavar) in Combination With Gemcitabine in Advanced Hepatocellular Carcinoma (HCC)
This study is to evaluate the efficacy and safety of Sorafenib in combination with Gemcitabine in patients with advanced/unresectable HCC.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)|
- To evaluate the efficacy (progression free survival (PFS)) of sorafenib in patients with advanced/unresectable HCC. [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2008|
|Study Completion Date:||August 2011|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
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
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.
|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|
|Principal Investigator:||Vichien Srimuninnimit, Assist.Prof.||Siriraj Hospital, Bangkok, Thailand|