Efficacy of Sirolimus In Liver Transplantation for Hepatocellular Carcinoma (HCC)
The purpose of this study is to evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival.
Drug: m-TOR inhibitor free
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase Ⅱ, Trial With Sirolimus-containing Versus mTOR-inhibitor Free Immunosuppression in Patients Undergoing Living Donor Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria|
- To evaluate recurrence-free survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]To evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival
- To evaluate the survival rate [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]The recurrence is defined by tumor recurrence in imaging study. The recurrence free survival will be calculated by Kaplan-Meier method.
- To evaluate the renal function [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Renal function will be evaluated by calculated GFR (Cockcroft-Gault method) at postoperative 6month, 12month, 18month, 24month, 30month, and 36month.
- To evaluate the safety with sirolimus [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Safety of sirolimus will be evaluated by the comparison of proportion of patients with serious adverse events during the follow-up period between two groups (m-TOR goup vs. m-TOR free group). Other minor side effects will be monitored and compared between two groups as well.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Active Comparator: m-TOR inhibitor free
Drug: m-TOR inhibitor free
Other Name: Rapamune
The Milan criteria were adopted in most of western countries for deceased donor allocation because they identify a subgroup of candidates with hepatocellular carcinoma (HCC) for whom transplant results are similar to those in patients transplanted for end- stage liver disease without HCC. There is a debate involving expanding the indications beyond the Milan criteria in living donor liver transplantation (LDLT). Some transplant surgeons argue that despite the poorer results, LDLT for advanced HCC may be justified, since donors voluntarily accept the risks of donor hepatectomy to dedicate a graft for HCC patients, who may otherwise have no effective treatment. Especially, in Korea where living donor liver transplantation (LDLT) is commonly performed, the expansion of Milan criteria is inevitable. Sirolimus is a macrolide antibiotic produced by Streptomyces hygroscopic that has demonstrated potent immunosuppressive activity in a number of studies. The efficacy of sirolimus as immunosuppressives has been demonstrated in randomized clinical trials in kidney transplantation. The use of sirolimus in liver transplantation is rapidly increasing from the standpoint of reducing the conventional calcineurin inhibitor toxicity. Sirolimus emerged as an effective alternative for patients with renal insufficiency related to calcineurin inhibitor toxicity. In recent studies, no differences have been observed with respect to rejection or major complications.The use of sirolimus in transplant patients is associated with a dose-dependent increase in serum cholesterol and triglycerides that may require treatment. In recent studies in liver transplant recipients using sirolimus as part of a primary immunosuppressive regimen, the occurrence of acute cellular rejection is relatively low. There is data suggesting that sirolimus is associated with hepatic artery thrombosis. Numerous current studies have shown that sirolimus may have inhibitory effects on the development of cancer. Immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of liver transplantation for HCC. If sirolimus shows some degree of anti-tumor effect in transplant recipients with advanced HCC, the indication of LDLT for advanced HCC can be expanded.Our hypothesis is that sirolimus based-regimen will improve the HCC recurrence free survival. If sirolimus-based protocol shows better recurrence free survival, the indication of LDLT for HCC can be expanded. LDLT can be one of the best treatment modalities for advanced HCC. The patients with advanced HCC can have benefit by liver transplantation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01374750
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Korea, Republic of|
|Principal Investigator:||Kwang-woong Lee||Seoul National University Hospital|