TACE-2: A Randomized Placebo-Controlled, Double Blinded, Phase III Trial of Sorafenib in Combination With Transarterial Chemoembolization in Hepatocellular Cancer
- To determine whether the addition of sorafenib tosylate to transarterial
chemoembolization (TACE) with doxorubicin-eluting beads, compared to TACE alone,
prolongs progression-free survival of patients with unresectable hepatocellular
- To determine if adding sorafenib tosylate to TACE prolongs overall survival of these
- To determine if the sorafenib tosylate regimen prolongs time to progression in these
- To determine acceptable toxicity related to the sorafenib tosylate regimen in these
- To determine the effects of the sorafenib tosylate regimen on disease response, in
terms of complete response, partial response, or stable disease, in these patients.
- To determine the effects of the sorafenib tosylate regimen on quality of life of these
- To determine if treatment with the sorafenib tosylate regimen reduces the frequency for
repeat TACE as measured by number of TACE procedures performed in 12 months.
- To establish a blood sample bank linked to this study for biomarker research (proteomic
and genomic analysis).
OUTLINE: This is a multicenter study. Patients are stratified according to randomizing
centers and serum alpha-fetoprotein levels (< 400 ng/mL vs ≥ 400 ng/mL). Patients are
randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral sorafenib tosylate twice daily in the absence of disease
progression or unacceptable toxicity. Beginning within 2-5 weeks after start of
sorafenib tosylate, patients undergo transarterial chemoembolization (TACE) with
doxorubicin-eluting beads. Patients may undergo additional sessions of TACE with
doxorubicin-eluting beads, in the absence of complete devascularization of the tumor(s)
(as assessed by follow-up contrast enhanced scan).
- Arm II: Patients receive oral placebo twice daily in the absence of disease progression
or unacceptable toxicity. Beginning within 2-5 weeks after start of placebo, patients
undergo TACE with doxorubicin-eluting beads as in arm I. Patients with disease
progression may cross over to the sorafenib tosylate arm at the discretion of the
treating clinician and are followed for survival.
Blood samples may be collected at baseline and periodically for pharmacogenetic and
pharmacokinetic studies. Patients complete EORTC QoL questionnaire (QLQ-C30) version 3 and
EORTC QLQ-HCC18 (a site-specific module for HCC) at baseline and periodically during the
After completion of study therapy, patients are followed up periodically for 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Tim Meyer, MD, BSc, MRCP, PhD
Royal Free Hospital