Sorafenib Plus Tegafur/Uracil (UFUR®) for Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma Clinical Trial

Official title: A Phase II Study of Sorafenib Plus Tegafur/Uracil for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma

Status Completed

Clinical Trial Summary

The prognosis for patients with metastatic or locally advanced hepatocellular carcinoma (HCC) is poor. The role of conventional systemic chemotherapy has been very limited because most chemotherapeutic agents are in-effective and relative toxic to HCC patients who tend to have poor organ function reserves due to liver cirrhosis. The molecular-targeted therapy, which aims at deranged signaling pathways of cancer cells or their microenvironment, holds promise for HCC.

Sorafenib (BAY 43-9006), a novel bi-aryl urea, is a potent inhibitor of VEGFR2 and Raf kinase. The clinical activity of sorafenib in HCC has been tested in a phase II study (Bayer study 10874), which enrolled a total of 137 advanced HCC patients. There were 4% of documented partial response, 5% of minor response, and 55% of stable disease. The 6- month progression -free for the cohort was 40%. Currently, there are two on-going large-scale randomized trials of sorafenib in advanced HCC patients worldwide.

Clinical Trial Description

The prognosis for patients with metastatic or locally advanced hepatocellular carcinoma (HCC) is poor. The role of conventional systemic chemotherapy has been very limited because most chemotherapeutic agents are in-effective and relative toxic to HCC patients who tend to have poor organ function reserves due to liver cirrhosis. The molecular-targeted therapy, which aims at deranged signaling pathways of cancer cells or their microenvironment, holds promise for HCC.

Sorafenib (BAY 43-9006), a novel bi-aryl urea, is a potent inhibitor of VEGFR2 and Raf kinase. The clinical activity of sorafenib in HCC has been tested in a phase II study (Bayer study 10874), which enrolled a total of 137 advanced HCC patients. There were 4% of documented partial response, 5% of minor response, and 55% of stable disease. The 6- month progression -free for the cohort was 40%. Currently, there are two on-going large-scale randomized trials of sorafenib in advanced HCC patients worldwide.In this study proposal, we propose to combine sorafenib with metronomic chemotherapy in the treatment of advanced HCC patients. It has been recently demonstrated that cytotoxic chemotherapy, when given in a low-dose, continuous, and uninterrupted way (i.e. the "metronomic" chemotherapy), inhibits tumor angiogenesis. The anti-angiogenesis effect of metronomic chemotherapy can be potentiated by combining the inhibitors of VEGF/VEGFR pathway. UFUR®, a composite drug composed of tegafur and uracil, is an orally active 5-fluorouracil (5-FU) preparation. The activity of tegafur/uracil in HCC has been tested in two relatively small-scale phase II studies, with objective tumor response rates ranging from 0~18%. Interestingly, tegafur and its metabolites, including γ-hydroxybutyric acid and γ-butyrolactone, have been shown to be potent inhibitors of angiogenesis in several preclinical models. Therefore, tegafur/uracil (UFUR®), which has potential anti-HCC activity and interesting anti-angiogenesis activity, is an ideal candidate drug to improve the efficacy of sorafenib in HCC. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

• NCT number: NCT00464919
• Study type: Interventional
• Source: National Taiwan University Hospital
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Completion date: March 2009