Sorafenib Plus Tegafur-uracil (UFT) Versus Sorafenib as First Line Systemic Treatment for Patients With Advanced Stage HCC, Unresectable & Not Eligible for Local Ablation and/or TACE

Advanced Hepatocellular Carcinoma Clinical Trial

Official title: A Phase II Trial of Sorafenib Plus Tegafur-uracil (UFT) vs. Sorafenib as First Line Systemic Treatment for Patients With Advanced Stage HCC, Unresectable & Not Eligible for Local Ablation &/or TACE

Status Terminated

Clinical Trial Summary

• Unlike the Asian and western regions, The vast majority of the Egyptian/Arabic Hepatocellular Carcinoma (HCC) patients are hepatitis C virus (HCV) associated.

• According to the SHARP study subgroup analysis, it seems that HCV associated HCC patients derive the max benefit of Sorafenib, the absolute gain between the Sorafenib arm & the placebo in m OS = 7 months, HR=0.58 (95% CI: 0.37-0.91).

• In spite of improvement in terms of overall survival (OS) and time to progression (TTP), in all studies where Sorafenib was compared to placebo, the Sorafenib arm was not accompanied by a significant volumetric reduction, and this may explains the lack of any symptomatic improvement (time to symptomatic progression (TTSP) almost identical)

• Reviewing the chemotherapy outcome, although there is no convincing evidence in survival benefit to patients with advanced HCC, however true shrinkage (reduction in tumor size), has been consistently reported although the magnitude of response is lacking consistency.

This indicates the need for coupling Sorafenib to a chemotherapeutic agent but:

• For patients with Hepatocellular Carcinoma, the toxicity profile of any chemotherapeutic agent of choice to be added to Sorafenib should be take in consideration

• The agent to be added to Sorafenib should be effective in terms of Tumor Shrinkage & with minimal toxicity regarding:

• Cardio-toxicity

• HFSR

• Diarrhea

• Hepato-toxicity

• Bone marrow suppression (although not relevant to the toxicity profile of Sorafenib, yet the HCC patients may have HCV related thrombocytopenia and variable degree of hypersplenism related pancytopenia)

Circulatory Overload (Hypertension) Why Tegafur-uracil (UFT)?

• Efficacy: For UFT, although the efficacy data in HCC are not as extensive as Doxorubicin, however in one phase II study UFT could improve survival when compared with conservative management.

• UFT Toxicity Profile:

In a phase III trial to asses the compare Efficacy & Safety of UFT with that of 5 FU in treatment of m CRC, Hematological toxicities were minimal (0% Grade ¾ leukopenia, neutropenia, febrile neutropenia, thrombocytopenia & was 3% for anemia), while the most commonly seen SE was grade I & II Diarrhea

•Accordingly UFT may be considered as a potential partner to Sorafenib in patients with advanced HCC.

Clinical Trial Description

n/a

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma, Hepatocellular

• NCT number: NCT01539018
• Study type: Interventional
• Source: Egyptian Society of Liver Cancer
• Status: Terminated
• Phase: Phase 2
• Start date: January 2012
• Completion date: January 2015