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

NCT02081755 | Enrolling By Invitation Phase 4 DMC

• 1 other identifier: 013-307
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 9

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Immunosuppressive Agents; Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Tumor recurrence sites

  Through Month 36

• Hepatitis C recurrence rate

  Through Month 36

• Renal function

  Through Month 36

• Acute cellular rejection

  Through Month 36

• Post-transplant diabetes

  Through Month 36

Study Arms (2)

Everolimus and Tacrolimus

EXPERIMENTAL

Everolimus Dosing: 1.5 mg BID (3.0 mg/day) Tacrolimus Dosing: 0.05 mg/kg BID

Drug: Everolimus; Drug: Tacrolimus

Tacrolimus and Myfortic or CellCept or Imuran

ACTIVE COMPARATOR

Myfortic: 360 mg to 1080 mg BID OR CellCept: 500 mg to 1500 mg BID OR Imuran: 0.5mk/kg to 2mg/kg QD AND Tacrolimus Dosing: 0.05 mg/kg BID

Drug: Tacrolimus; Drug: Myfortic; Drug: CellCept; Drug: Imuran

Interventions

Everolimus DRUG

Everolimus Dosing: 1.5 mg BID (3.0 mg/day) for 12 months

Also known as: Zortress, Afinitor

Everolimus and Tacrolimus

Tacrolimus DRUG

Tacrolimus Dosing: 0.05 mg/kg BID for 12 months

Also known as: Prograf

Everolimus and Tacrolimus; Tacrolimus and Myfortic or CellCept or Imuran

Myfortic DRUG

Myfortic®: 360 mg to 1080 mg BID for 12 months

Also known as: Mycophenolic Acid

Tacrolimus and Myfortic or CellCept or Imuran

CellCept DRUG

CellCept: 500 mg to 1500 mg BID for 12 months

Also known as: Mycophenolate Mofetil

Tacrolimus and Myfortic or CellCept or Imuran

Imuran DRUG

0.5 mg/kg to 2 mg/kg QD for 12 months

Also known as: Azathioprine

Tacrolimus and Myfortic or CellCept or Imuran

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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• Patients who receive sirolimus (Rapamune) any time prior to randomization will be withdrawn from the study.

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (9)

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Northwestern University School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Tennessee- Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Everolimus; Tacrolimus; Mycophenolic Acid; Azathioprine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Goran Klintmalm, MD, PhD

  Baylor Health Care System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 7, 2014
• Study Start: March 1, 2014
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)