Prophylaxis against liver transplant rejection in patients undergoing liver transplantation for hepatocellular carcinoma (HCC) MedDRA version: 8.1 Level: LLT Classification code 10050434
Conditions
Interventions
Product Name: Sirolimus
Product Code: AY-22989
Pharmaceutical Form: Coated tablet
INN or Proposed INN: sirolimus
Current Sponsor code: AY-22989
Other descriptive name: rapamycin
Concentration unit: mg
Sponsors
Regensburg University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Deceased Donor Liver Transplantation The study includes all patients eligible for OLT as outlined by each of the participating centers fulfilling the following criteria: 1. Age 18 years and older 2. Histologically proven HCC before randomisation* 3. Signed, written informed consent *Individual patients who were treated pre-OLT for histologically proven HCC by for example chemoembolisation, radiofrequency ablation, or percutaneous ethanol installation, may show tumor reduction, or even complete necrosis. If there is complete tumor necrosis, histologic confirmation of HCC-post OLT will not be possible. In these cases, patients with a pretransplant histologic diagnosis of HCC may still be included in the study. However, patients with a complete biological tumor response will be down-staged and therefore stratified into the group considered within Milan criteria. In all patients with a pre-OLT histologic proof of HCC, and an incomplete tumor response following pretreatment, stratification will be solely performed according to the final postoperative histology. Living-related liver transplantation The study will also include living-related liver transplants (LRLT) performed in HCC recipients. Inclusion criteria 1-3 (listed above) will apply in the same way. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Multiple organ recipients 2. Known hypersensitivity to sirolimus or its derivatives 3. Hyperlipidemia refractory to optimal; medical management (cholesterol >300 mg/dL; triglycerides >350 mg/dL) * 4. Evidence of significant local or systemic infection 5. Known HIV-positive patients * 6. Platelets<75,000/cubic mm * 7. Women of child bearing potential not willing to take contraception 8. Patients with non-HCC malignancies within the past 5 years, excluding successfully treated squamous cell carcinoma and basal cell carcinoma of the skin 9. Extrahepatic HCC tumor manifestation. ** 10. Patients with psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule 11. Patients under guardianship (e.g. patients who are not able to freely give their informed consent) 12. Patients receiving mTOR inhibitors prior to day 29 post-OLT. * Based on the last data available before randomisation. ** Including tumor formations found in the extrahepatic portal vein.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether sirolimus-containing immunosuppression will prolong recurrence-free survival as compared to mTOR-inhibitor-free immunosuppression (or equivalently, whether sirolimus will decrease risk of recurrence) in patients undergoing liver transplantation for hepatocellular carcinoma (HCC). ;Secondary Objective: The secondary objectives include: 1. Patient overall survival (5 year). 2. Incidence of de novo malignancy. 3. Liver allograft function. 4. Time to HCC recurrence. 5. Tumor number and size at time of HCC recurrence. 6. Tumor progression rate in patients maintained on immunosuppression. 7. HCV and HCB recurrence. 8. Disease free and overall survival in the high risk group. 9. Disease free and overall survival in the low risk group.;Primary end point(s): HCC recurrence-free patient survival (Section 3.4 (Statistical Methods) of the protocol has the following wording regarding the definition of recurrence-free survival: The primary efficacy endpoint is recurrence-free survival (RFS). RFS is defined as the time interval between the date of liver transplantation and the date of recurrence or death (as first event), or, in patients without recurrence, the date of the last follow-up (i.e. patients who are alive and recurrence-free at the time of analysis will be censored for recurrence-free survival at the time of their last contact.) HCC recurrence is defined as either histologically-proven tumor recurrence, or unequivocal tumor recurrence detected by radiologic means, generally in combination with a renewed increase in the tumor marker AFP. Strong clinical evidence for HCC recurrence like beta-symptoms, weight loss, inappetence, pruritus and ascites should be considered as first signs, followed by further diagnostic action. In accordance to the Barcelona-Criteria, concluded at the Barcelona-2000 EASL Conference (published in: Journal of Hepatology, 35(2001): 421-430), radiologic criteria of HCC recurrence include two coincident imagi | — |
Countries
Austria, Belgium, Finland, Italy, Norway, Spain, Sweden, United Kingdom
Outcome results
None listed