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

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.

Conditions

• Advanced Hepatocellular Carcinoma

Interventions

DRUG

Sorafenib

Sorafenib 400 mg p.o. twice daily until progression or intolerable toxicity alone.

DRUG

sorafenib plus tegafur-uracil

Sorafenib 400 mg p.o. twice daily until progression or intolerable toxicity and TEGAFUR-URACIL 125mg/m2 PO BID For 4 weeks and to be repeated on day 36 till progression or intolerance

Sponsors & Collaborators

• Egyptian Society of Liver Cancer

  lead OTHER

Principal Investigators

• Hamdy Abdelazim, MD/PhD · Cairo University

• Hesham Atef, MD/PhD · Cairo University

• Ashraf Abdelaziz, MD/PhD · Cairo University

• Mohammed Shaker, MD/PhD · Ain Shams University

• Imam Waked, MD/PhD · Monofeiya university

• Heba Elzawahry, MD/PhD · Cairo university, national cancer institute

• Mohammed Ezz alarab, MD/PhD · NTMRI

• Omar Abdel-Rahman, M.D./M.Sc. · Ain Shams University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2015-01-31

Completion

2015-01-31

Countries

• Egypt

Study Locations