A Phase I Open Label/Phase II Randomized, Double-Blind, Multicenter Trial Investigating the Combination of Everolimus and TransArterial ChemoEmbolization (TACE) With Doxorubicin in Patients With Hepatocellular Carcinoma
OBJECTIVES:
- Determine the recommended dose of everolimus in patients with hepatocellular carcinoma
(HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads
(TACE). (Phase I)
- Determine the efficacy and tolerability of everolimus in patients with HCC treated with
TACE as compared to TACE alone. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase
II study.
- Phase I: Patients receive oral everolimus once daily in the absence of disease
progression or unacceptable toxicity. Beginning 7 days after the start of everolimus
patients undergo transarterial chemoembolization (TACE) comprising doxorubicin-eluting
beads into the hepatic artery followed in 4 weeks by an MRI. If viable tumor is found
patients undergo another TACE treatment continuing every 4 weeks for up to 5
treatments.
- Phase II: Patients are stratified according to center, age (≤ 60 vs > 60 years), and
number of lesions (≤ 3 vs > 3). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral placebo once daily for up to 12 months and undergo
TACE comprising doxorubicin-eluting beads as in phase I at the maximum tolerated
dose (MTD).
- Arm II: Patients receive oral everolimus once daily for up to 12 months and
undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
In both arms, patients receive treatment for up to 12 months in the absence of disease
progression or unacceptable toxicity.
Blood samples are collected periodically for analysis of AFP tumor markers. Patients also
complete quality of life questionnaires, Health Economic Assessment, and EQ5D questionnaires
at baseline and periodically during the study.
After completion of study treatment, patients are followed on day 30, and then every 3
months.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Dose-limiting toxicity (Phase I)
Dose limiting toxicity (DLT) (observed within the first TACE period)
after 6 weeks from registration
Yes
Jean-Francois Dufour, MD
Study Chair
University Hospital Inselspital, Berne
Switzerland: Swissmedic
SAKK 77/09
NCT01009801
February 2010
September 2013
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