Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer

Status: Closed to Accrual

Description

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.

Eligibility Criteria

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

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

Locations & Contacts

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: Active
Name Not Available

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Name Not Available

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase IV

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor University Medical Center

Trial IDs

Primary ID 013-307
Secondary IDs NCI-2017-02502
Clinicaltrials.gov ID NCT02081755