Transarterial Chemoembolization Using Doxorubicin Beads With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether transarterial chemoembolization using doxorubicin-eluting beads is more effective when given with or without sorafenib tosylate in treating patients with liver cancer that cannot be removed by surgery.
PURPOSE: This randomized phase III trial is studying giving transarterial chemoembolization using doxorubicin-eluting beads and sorafenib tosylate to see how well it works compared with giving transarterial chemoembolization using doxorubicin-eluting beads and a placebo in treating patients with liver cancer that cannot be removed by surgery.
Drug: doxorubicin-eluting beads
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: quality-of-life assessment
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||TACE-2: A Randomized Placebo-Controlled, Double Blinded, Phase III Trial of Sorafenib in Combination With Transarterial Chemoembolization in Hepatocellular Cancer|
- Progression-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Disease control (complete or partial response or stable disease) [ Designated as safety issue: No ]
- Quality of life [ Designated as safety issue: No ]
|Study Start Date:||November 2010|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
- 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 carcinoma.
- To determine if adding sorafenib tosylate to TACE prolongs overall survival of these patients.
- To determine if the sorafenib tosylate regimen prolongs time to progression in these patients.
- To determine acceptable toxicity related to the sorafenib tosylate regimen in these patients.
- 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 patients.
- 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 study.
After completion of study therapy, patients are followed up periodically for 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
|Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust||Recruiting|
|Birmingham, England, United Kingdom, B15 2TH|
|Contact: Contact Person 44-121-472-1311|
|Bristol Royal Infirmary||Recruiting|
|Bristol, England, United Kingdom, BS2 8HW|
|Contact: Contact Person 44-117-923-0000|
|Aintree University Hospital||Recruiting|
|Liverpool, England, United Kingdom, L9 7AL|
|Contact: Contact Person 44-151-525-5980|
|King's College Hospital||Recruiting|
|London, England, United Kingdom, SE5 9RS|
|Contact: Contact Person 44-20-3299-9000|
|Royal Marsden - London||Recruiting|
|London, England, United Kingdom, SW3 6JJ|
|Contact: Contact Person 44-20-7352-8171|
|Royal Free Hospital||Recruiting|
|London, England, United Kingdom, NW3 2QG|
|Contact: Contact Person 44-20-7794-0500|
|Queen's Medical Centre||Recruiting|
|Nottingham, England, United Kingdom, NG7 2UH|
|Contact: Contact Person 44-115-924-9924|
|Southampton General Hospital||Recruiting|
|Southampton, England, United Kingdom, SO16 6YD|
|Contact: Contact Person 44-23-8079-8751|
|Principal Investigator:||Tim Meyer, MD, BSc, MRCP, PhD||Royal Free Hospital|