A Phase I/II Study of Sorafenib With Combination of Thalidomide in Advanced or Metastatic Hepatocellular Carcinoma
This is a non-randomized, open-labeled, single-arm, multi-center, phase I /II clinical
study. The Phase I purpose of this study is to determine the maximal tolerable dose (MTD) of
thalidomide (THADO®) in combination with fixed dose of sorafenib (NEXAVAR®) for the
treatment of advanced or metastatic HCC, and the dose-limiting toxicity (DLT) profiles and
other toxicity profiles in patients receiving fixed dose of sorafenib (NEXAVAR®) plus
escalating dose of thalidomide (THADO). The Phase II primary objective of this study is to
determine the disease control rate (complete response + partial response + stable disease)
for at least 4 months of sorafenib (NEXAVAR®) plus phase I determined MTD of thalidomide
(THADO®) in patients with advanced or metastatic HCC. The Phase II secondary objective of
this study is to determine the objective tumor response rate, the time to tumor progression,
the progression-free survival, the overall survival, and the safety and adverse event
profiles, the changes of circulating biomarkers relating to angiogenesis and their
correlation with disease control rate.
The sample size are required up to 24 patients for the phase I study and 53 patients for the
phase II study.
Sorafenib (NEXAVAR®): supplied to Good Manufacturing Practice standards by Bayer Health
Care, Taiwan as a film-coated tablet, each of which contains sorafenib tosylate (274mg)
equivalent to 200 mg of sorafenib. Thalidomide (THADO®): supplied to Good Manufacturing
Practice standards by TTY Biopharm Co., Ltd. as a white-yellow capsule, each of which
contains 50 mg of thalidomide.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Terms of efficacy assessment: objective tumor response, overall survival, progression-free survival. Terms of safety assessment: adverse effects, laboratory values.
The overall survival will be measured from the time the patient has started protocol treatment to the date of the patient's death. 2. An interim analysis of safety profiles will be reviewed by safety committee.
Chung Hu Chan, MD, PHD
National Health Research Institutes, Taiwan
Taiwan: Department of Health