A Randomized, Controlled Phase III Trial of Sorafenib With or Without cTACE in Patients With Advanced HCC

A Randomized, Controlled Phase III Trial of Sorafenib With or Without Conventional Transarterial Chemoembolization in Patients With Advanced Hepatocellular Carcinoma (STAH Study)

This is a randomized, multi-center, open-labeled, phase III study in patients with advanced HCC. A total of 338 patients will be randomized (1:1) into one of the two treatment arms, to receive sorafenib with (Arm Combination-treatment; Arm C) or without (Arm Sorafenib alone treatment; Arm S) cTACE.

All the patients will be initially given sorafenib within 72 hours after the randomization. Treatment should continue until the criteria for treatment discontinuation are met.

After the treatment period, patients will undergo follow up for survival every 12 weeks (±7 days) from the last dose, and the survival follow up will be performed for at least 1.5 years after the last patient's last treatment.

The superiority of the Arm C (cTACE+Sorafenib) over the Arm S (Sorafenib) in the OS period will be verified in the ITT set and FAS using a stratified log-rank test. Stratification factors consist of mUICC stage (III vs. IV), Vascular invasion (none and Vp1-2 vs. Vp3-4 and any other presence), Child-Pugh score (5 vs. 6-7), serum AFP level (≥200 ng/mL vs. <200 ng/mL). The significance level is 5% (one-sided).

Inclusion Criteria:

To be eligible to participate in the study, patients must meet the following criteria:

1. Signed written informed consent
2. Clinical or histological diagnosis of HCC based on the guidelines of the Korean Liver Cancer Study Group and the National Cancer Center Korea
3. At least one typical enhanced index lesion in the liver that is bi-dimensionally measurable by multiphasic spiral CT scan or dynamic contrast-enhanced MRI, and size of largest tumor is 15 cm or less at enrollment.
4. Tumor conditions confirmed by abdominal imaging (contrast enhanced CT ± MRI) and chest imaging (CT) performed within 4 weeks prior to the treatment initiation:
5. Age of at least 20 years.
6. ECOG Performance Status of 0, 1 or 2.
7. Child-Pugh class A or B (Child-Pugh score ≤ 7).
8. Life expectancy of at least 16 weeks.
9. Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements (no transfusion, no restoration), conducted within 14 days prior to screening:
10. Female patients at least 1 year postmenopausal, surgically sterile or those of childbearing potential must have a negative urine pregnancy test within 14 days prior to the first treatment, and have to use at least one medically acceptable and effective contraceptive method for the last 2 months prior to Screening Visit: methods of effective contraception result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as a barrier method (implant, injectable contraceptives, oral contraceptives, intrauterine contraceptive device), hormonal IUD, sexual abstinence or vasectomized partner.

Exclusion Criteria: