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

Official Title:

A 36 Month Multi-center, Open Label, Randomized, Comparator Study to Evaluate the Efficacy and Safety of Everolimus Immunosuppression Treatment in Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 4 Interventional 18 Years and older Baylor Research Institute 013-307
NCT02081755
Enrolling patients

Study Design:


Principal Investigator

Professor of Clinical Surgery 
Division of Transplant Surgery
Associate Program Director,
UCSF General Surgery Residency Program

Clinical Research Coordinator

UCSF Medical Center at Parnassus
(415) 514-0192 Phone

Trial 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. 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

Inclusion Criteria:
Screening
  • Listed as a patient within the top 20 on the wait list at each study site/center
  • 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
Randomization
  • HCC in the explanted liver showing a tumor burden exceeding Milan criteria, and/or
    poorly differentiated tumors based on histology exam, and/or with microscopic
    vascular invasion based on pathology reports and/or alpha- fetoprotein (AFP) >200
    IU/mL taken at the most recent time point prior to randomization.
  • For patients with a history of any hepatic vessel thrombosis, occlusion, stent
    placement, or major reconstruction of liver vessels, must have a Doppler ultrasound
    1-2 days prior to randomization to rule out any hepatic vessel complication,
    including hepatic arterial thrombosis (HAT).
  • Patient is able to take oral medications.
  • Pathology findings of viable tumor.
  • Downstaged tumors, if upon explant, meet randomization criteria.
  • Functioning liver allograft at the time of randomization
Exclusion Criteria:
Screening
  • Past or present malignancy within the last 5 years (other than excised basal cell
    carcinoma and/or HCC satisfying the Milan criteria).
  • 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.
  • 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.
Randomization
  • Complete necrosis of HCC nodules on explant.
  • 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.
  • Incomplete wound healing at the surgical site including infections, dehiscence or a
    condition that requires the wound to remain open.
  • 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.
  • Major/reconstructed hepatic vein, portal vein or inferior vena cava at any time prior
    to randomization.
  • Proteinuria greater than 2 grams

Detailed Description

The study population will consist of approximately 336 patients (224 Everolimus and
Tacrolimus and 112 Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil). Initial
screening criteria will include patients 18 years or older who are candidates to receive a
primary orthotopic liver transplant (from deceased or living donor). Within 7 - 10 days
post-transplant, patients will be re-evaluated for eligibility for randomization. The
criteria include the presence of hepatocellular carcinoma in the explant as determined by
pathology evaluation, pathology review for tumor burden, presence of microvascular invasion,
no evidence of hepatic vessel complications, functioning liver allograft, able to take oral
medications and no systemic infection or delayed wound healing.
Subjects will remain in study treatment until Month 24 at which time the subject and
investigator will determine the preferred immunosuppressive regimen. Subjects will be
followed for an additional 12 months for outcome data as described above.

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 2/7/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
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