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

• Status: Unknown status
• Trial end date: 2021-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor Research Institute
• Treatments: Azathioprine; Everolimus; Mycophenolate mofetil; Mycophenolic Acid; Sirolimus; Tacrolimus

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 Exclusion Criteria:

• Patients who receive sirolimus (Rapamune) any time prior to randomization will be withdrawn from the study.

• Patients who develop clinically significant systemic infections requiring active use of IV antibiotics any time prior to randomization.

• Wound healing problem, per Investigator's assessment, that would make the patient ineligible for study randomization

• Confirmed presence of a thrombosis in a major hepatic artery(s), major hepatic vein(s), portal vein or inferior vena cava via Doppler ultrasound or other imaging obtained prior to randomization.

• Proteinuria greater than 2 grams/24 hours.

• Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive everolimus or be randomized into the study.