Sirolimus-Based Immunosuppression Therapy in OLT for Patients With HCC Exceeding Milan Criteria

November 5, 2007 updated by: Fudan University

A Prospective Randomised, Open-Labeled Study Comparing Sirolimus Versus FK506 In OLT for Patients With HCC Exceeding Milan Criteria

The purpose of this study is to evaluate the influence of sirolimus on outcome after OLT for HCC exceeding Milan criteria.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in Asia and Africa. Although the first-line therapy for HCC is liver resection, the concomitant cirrhosis often leaves orthotopic liver transplantation (OLT) rather than liver resection as the only potentially curative option. The risk of recurrence is the major concern in patients transplanted for HCC. It has been demonstrated that utilizing more restrictive selection criteria before submitting cirrhotic patients with HCC to liver transplantation is associated with a better outcome. The Milan criteria (one nodule ≤5 cm or 2-3 nodules all <3 cm, without macroscopic vascular invasion and extrahepatic spreading)provide a simple means of selecting patients with HCC for transplantation with a low risk (≈10%) for recurrence. However, the benefit of OLT for patients with HCC within the Milan criteria is opposed by a critical organ shortage, which lengthens the waiting time and thus allows tumor progression during the waiting period. Nearly one third of patients who have a transplant for HCC fall outside the Milan criteria on the basis of pathological findings in the explanted liver, and had a higher risk of tumor recurrence.This led to a dramatic decline in overall and disease-free survival, from 71-85% to 40-50%, and from 65-78% to 27-30%, respectively.

Although it can be hypothesized that the pharmacologic immunosuppression required after liver transplantation for HCC may be accelerated tumor recurrence and metastasis, recent reports have suggest that not all immunosuppressive drugs necessarily promote HCC recurrence in transplant recipients. Sirolimus has emerged as a new, potent immunosuppressive agent which unlike other immunosuppressants [cyclosporine (CsA), tacrolimus (FK506), and azathioprine (AZA)] has potent antitumor activity in vitro and in vivo. The immunosuppressive and antitumor effects of sirolimus share a common mechanism of action. Sirolimus inhibits the mammalian target of sirolimus (mTOR), which prevents acute graft rejection mediated by interleukin-2 and could block other cytokine signal transduction, thus directly inhibits tumor cell proliferation and angiogenesis. And the most important is that the antitumor activity of SRL has been shown at the same concentrations as maintenance target levels in posttransplant patients.

Thus, it seems reasonable to speculate that sirolimus could simultaneously contribute to inhibition of tumor recurrence and preventing of rejection in OLT for patients with HCC.

Study Type

Interventional

Enrollment (Anticipated)

220

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200032
        • Recruiting
        • Liver Cancer Institute and Zhongshan Hospital, Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The major organ (liver,heart, lung and kidney) function after OLT was normal.
  • Pathologically proved HCC before randomisation .
  • Tumor exceeding the Milan criteria (one nodule ≤5 cm or 2-3 nodules all <3 cm, without macroscopic vascular invasion and extrahepatic spreading).
  • Signed, written informed consent.

Exclusion Criteria:

  • Extrahepatic metastasis, nodal involvement, perioperative deaths (within 30 days after operation), and tumor thrombi in the proximal main trunk of the portal vein and / or vena cava
  • History of cardiac disease.
  • Active clinically serious infection (>grade 2 Nation Cancer Institute NCI-CTCAE version 3.0).
  • Known history of human immunodeficiency virus (HIV) infection.
  • Any condition that is unstable or which could jeopardize the safety of the patient and his / her compliance in the study.
  • Pregnant or breast-feeding patients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 2, III ,intervention
Drug: sirolimus
given at an initial dose of 3 mg/m2, and adjusted over time to achieve steady-state whole-blood trough levels of approximately 5-8 ng/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival
Time Frame: 3-,5-year
3-,5-year

Secondary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: 3-,5-year
3-,5-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Study Director: Jia Fan, MD, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, China.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Study Completion (Anticipated)

August 1, 2013

Study Registration Dates

First Submitted

November 5, 2007

First Submitted That Met QC Criteria

November 5, 2007

First Posted (Estimate)

November 6, 2007

Study Record Updates

Last Update Posted (Estimate)

November 6, 2007

Last Update Submitted That Met QC Criteria

November 5, 2007

Last Verified

October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZSH-LCI-FJ-0002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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