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)
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the efficacy (progression free survival (PFS)) of sorafenib in patients with advanced/unresectable HCC.
Vichien Srimuninnimit, Assist.Prof.
Siriraj Hospital, Bangkok, Thailand
Thailand: Food and Drug Administration