A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Background: The potential anti-cancer effects of mammalian target
of rapamycin (mTOR) inhibitors are being intensively studied. To
date, however, few randomised clinical trials (RCT) have been
performed to demonstrate antineoplastic effects in the pure
oncology setting, and at present, no oncology endpoint-directed RCT
has been reported in the high-malignancy risk population of
immunosuppressed transplant recipients. Interestingly, since mTOR
inhibitors have both immunosuppressive and anti-cancer effects,
they have the potential to simultaneously protect against
immunologic graft loss and tumour development. Therefore, we
designed a prospective RCT to determine if the mTOR inhibitor
sirolimus can improve hepatocellular carcinoma (HCC)-free patient
survival in liver transplant (LT) recipients with a pre-transplant
diagnosis of HCC. Methods/Design: The study is an open-labelled,
randomised, RCT comparing sirolimus-containing versus
mTOR-inhibitor- free immunosuppression in patients undergoing LT
for HCC. Patients with a histologically confirmed HCC diagnosis are
randomised into 2 groups within 4-6 weeks after LT; one arm is
maintained on a centre-specific mTOR-inhibitor- free
immunosuppressive protocol and the second arm is maintained on a
centre-specific mTOR-inhibitor- free immunosuppressive protocol for
the first 4-6 weeks, at which time sirolimus is initiated. A
2(1/2)-year recruitment phase is planned with a 5-year follow-up,
testing HCC-free survival as the primary endpoint. Our hypothesis
is that sirolimus use in the second arm of the study will improve
HCC-free survival. The study is a non-commercial
investigator-initiated trial (IIT) sponsored by the University
Hospital Regensburg and is endorsed by the European Liver and
Intestine Transplant Association; 13 countries within Europe,
Canada and Australia are participating.