NCT03500848

Brief Summary

This is a multicenter, open-label, randomized, controlled clinical trial, in order to compare sirolimus-based (tacrolimus-free) versus tacrolimus-based (sirolimus-free) immunosuppression regimen for Hepatocellular Carcinoma (HCC) patients after liver transplantation.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
130

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started May 2018

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 29, 2018

Completed
20 days until next milestone

First Posted

Study publicly available on registry

April 18, 2018

Completed
13 days until next milestone

Study Start

First participant enrolled

May 1, 2018

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2023

Completed
Last Updated

April 18, 2018

Status Verified

April 1, 2018

Enrollment Period

5.1 years

First QC Date

March 29, 2018

Last Update Submit

April 16, 2018

Conditions

Keywords

Liver transplantationSirolimusTacrolimusHCC recurrence free survival

Outcome Measures

Primary Outcomes (1)

  • HCC recurrence free survival

    The primary endpoint is defined as HCC recurrence-free time interval between the date of liver transplantation and the date of HCC recurrence or death; patients who are alive and recurrence-free at the end of month 36 will be censored at the time of their last follow-up date. HCC recurrence can be determined during the entire follow-up period.

    Randomization to Month 36

Secondary Outcomes (5)

  • Overall survival

    Randomization to Month 36

  • Incidence of acute rejection

    Randomization to Month 36

  • Treatment failures defined as introduction of Tacrolimus to experimental group

    Randomization to Month 36

  • Graft survival

    Randomization to Month 36

  • Incidence of adverse events

    Randomization to Month 36

Study Arms (2)

Tacrolimus-based group

ACTIVE COMPARATOR

Tacrolimus-based immunosuppression regimen: Tacrolimus+MMF and/or steroids

Drug: TacrolimusDrug: MMF and/or steroids

Sirolimus-based group

EXPERIMENTAL

Sirolimus-based immunosuppression regimen: Tacrolimus (Tacrolimus elimination 30 (± 5) days post LT)+Sirolimus+MMF and/or steroids

Drug: Tacrolimus (Tacrolimus elimination)Drug: SirolimusDrug: MMF and/or steroids

Interventions

Tacrolimus will be started between 3 and 7 days post-transplantation and continued after randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The tacrolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. Tacrolimus trough levels are targeted to be maintained at 8-15ng/ml until Month 6. After Month 6, the dose will be adjusted over time to maintain steady-state tacrolimus trough blood levels of approximately 5-10 ng/mL.

Also known as: FK-506, Fujimycin, Prograf, Protopic, Advagraf
Tacrolimus-based group

Tacrolimus will be started between 3 and 7 days post-transplantation at a dose of 1.0 mg twice a day (bid, 2 mg daily dose) for 30 (± 5) days and eliminated when randomization is done.

Also known as: FK-506, Fujimycin, Prograf, Protopic, Advagraf
Sirolimus-based group

Within 24 hours of randomization, sirolimus will be started at a dose of 2.0 mg once a day. The sirolimus trough level is measured twice a week for 1 month, followed by trough level once a month thereafter. The dose will be adjusted over time to maintain steady-state sirolimus trough blood levels of approximately 4-10 ng/mL.

Also known as: Rapamune
Sirolimus-based group

For patients in both groups, MMF and/or steroids are initiated at or prior to the time of liver transplantation according to local practice. Steroids reduction is encouraged by 3 months post liver transplantation.

Also known as: Mycophenolate mofetil
Sirolimus-based groupTacrolimus-based group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Recipients who are 18-65 years of age
  • Histologically proven HCC before randomization
  • Recipients who have been initiated on an immunosuppressive regimen that contains tacrolimus, 3-7 days post-transplantation
  • Allograft is functioning at an acceptable level by the time of randomization as defined by protocol specific laboratory values
  • Ability and willingness to provide written informed consent and adhere to study regimen

You may not qualify if:

  • Patients with non-HCC malignancies within the past 5 years
  • Patients who are multiple-organ recipients
  • Patients who are known HIV-positive patients
  • Patients who have received mTOR inhibitors prior to day 30 after liver transplantation
  • Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients
  • Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drug
  • Patients with a psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510282, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

First Affiliated Hospital, Sun Yat-Sen University

Guanzhou, Guangdong, 510080, China

Location

MeSH Terms

Interventions

TacrolimusSirolimusMycophenolic Acid

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipids

Study Officials

  • Kebo Zhong, M.D

    Department of Heptobiliary Surgery II, Zhujiang Hospital, Southern Medical University, China

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Peihua Cao, Ph.D

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Post-doctoral Fellow

Study Record Dates

First Submitted

March 29, 2018

First Posted

April 18, 2018

Study Start

May 1, 2018

Primary Completion

May 31, 2023

Study Completion

May 31, 2023

Last Updated

April 18, 2018

Record last verified: 2018-04

Locations