Carcinoma, Hepatocellular
Conditions
Keywords
Immunosuppressive Agents, Liver Transplantation
Brief summary
This study is a prospective Phase IV study to determine if the use of Everolimus results in lower liver tumor recurrence and improved patient and graft survival after liver transplant for hepatocellular carcinoma (HCC). The immunosuppressive comparators will be Everolimus and Tacrolimus therapy compared to Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine. Primary outcomes data is disease free survival (the time from randomization to HCC recurrence or death). Secondary outcomes are rate of recurrence of Hepatitis C, problems related to wound healing, hernia repair within the first 12 months, hepatic arterial thrombosis, renal function, acute cellular rejection, post-transplant diabetes, hypertension, and hyperlipidemia.
Detailed description
The study population will consist of approximately 336 patients (224 Everolimus and Tacrolimus and 112 Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine). Initial screening criteria will include the presence of hepatocellular carcinoma in patients 18 years or older who are candidates to receive a primary orthotopic liver transplant (from deceased or living donor). Within 7 - 12 days post-transplant, patients will be re-evaluated for eligibility for randomization. The criteria include: pre-transplant imaging that shows HCC disease exceeding Milan criteria; pathology review for tumor burden and/or presence of microvascular invasion; AFP \>200IU/mL; pre-transplant ablation or resection with HCC recurrence; progression or new tumors; evaluation to rule out any hepatic vessel complication. Subjects will remain in study treatment until Month 12 at which time the subject and investigator will determine the preferred immunosuppressive regimen. Subjects will be followed for an additional 24 months for outcome data as described above.
Interventions
Sponsors
Baylor Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Screening Inclusion Criteria: * Have a diagnosis of hepatocellular carcinoma (HCC) and high risk for HCC recurrence * Able to provide written informed consent * Male and female patients of any race, 18 years or older * De novo recipients of a primary orthotopic liver transplant from a deceased or living donor * Patients willing to comply with study requirements * Women of child-bearing potential (WOCBP) must agree to use an effective method(s) of contraception during treatment and during the post treatment follow-up period Screening
Exclusion criteria
* Past or present malignancy within the last 5 years. * Severe infection considered by the local site investigator to be unsafe for study participation. * Use of other investigational drugs at the time of screening or within the last 30 days. * Patients scheduled for a combined transplant (such as liver-kidney), or having a previous solid organ, bone marrow, or autologous islet cell transplant. * Recipients of donor/recipient ABO incompatible grafts. * Recipients of organs from human immunodeficiency virus (HIV) or HBsAg positive donors. * Macrovascular tumor invasion. * Proteinuria greater than 2 grams/24 hours. * Conditions which can result in impaired absorption, distribution, metabolism or excretion of the study treatment. * Patients with non-infectious pneumonitis. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. * Women of child-bearing potential (WOCBP) not practicing an effective method(s) of contraception. * Patients who receive sirolimus (Rapamune®) as part of their transplant immunosuppression regimen Randomization Screening Inclusion Criteria : \- For patients with a history of any hepatic vessel thrombosis, occlusion, stent placement, or major revision of liver vessels, must have a Doppler ultrasound prior to randomization to rule out any hepatic vessel complication, including hepatic arterial thrombosis (HAT). Randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first. | Through Month 36 |
Secondary
| Measure | Time frame |
|---|---|
| Hypertension | Through Month 36 |
| Hyperlipidemia | Through Month 36 |
| Wound healing and associated risk factors | Through Month 36 |
| Hernia repair | Through Month 36 |
| Hepatic arterial thrombosis | Through Month 36 |
| Tumor recurrence sites | Through Month 36 |
| Hepatitis C recurrence rate | Through Month 36 |
| Renal function | Through Month 36 |
| Post-transplant diabetes | Through Month 36 |
| Acute cellular rejection | Through Month 36 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGoran Klintmalm, MD, PhD
Baylor Health Care System
Outcome results
None listed