NCT00355862

Brief Summary

The purpose of this study is to determine the safety and efficacy of sirolimus-based immunosuppressive therapy in patients following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), with regard to HCC recurrence-free patient survival.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
525

participants targeted

Target at P75+ for phase_3 hepatocellular-carcinoma

Timeline
Completed

Started Jan 2006

Longer than P75 for phase_3 hepatocellular-carcinoma

Geographic Reach
1 country

1 active site

Status
completed

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

Study Start

First participant enrolled

January 1, 2006

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

July 24, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 25, 2006

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
5.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

July 30, 2014

Status Verified

July 1, 2009

Enrollment Period

3.2 years

First QC Date

July 24, 2006

Last Update Submit

July 29, 2014

Conditions

Hepatocellular Carcinoma

Keywords

SirolimusmTORHCC-recurrence free survivalLiver transplant recipientsHCC recurrence free survival

Outcome Measures

Primary Outcomes (1)

  • Recurrence free survival

    5 year follow up after last patient in

Study Arms (2)

1

ACTIVE COMPARATOR

Center specific immunosuppressive regimen (mTOR inhibitor free)

Drug: CNI, MMF, Steroids, Aza etc. (mTOR inhibitor free)

2

EXPERIMENTAL

Sirolimus containing regimen

Drug: Sirolimus

Interventions

CNI, MMF, Steroids, Aza etc. (mTOR inhibitor free)DRUG

center specific therapeutic regimen without mTOR inhibition

Also known as: Cyclosporine, Tacrolimus, Azathioprine, MMF, Prednisolone, etc
1
SirolimusDRUG

Sirolimus based immunosuppression

Also known as: Rapamune
2

Eligibility Criteria

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

You may qualify if:

  • Age 18 years and older
  • Histologically proven HCC before randomisation
  • Signed, written informed consent

You may not qualify if:

  • Multiple-organ recipients.
  • Known hypersensitivity to sirolimus or its derivatives.
  • Hyperlipidemia refractory to optimal medical management. (cholesterol \>300 mg/dL; triglycerides \>350 mg/dL).\*
  • Evidence of significant local or systemic infection.
  • Known HIV-positive patients.\*
  • Platelets \<75,000/cubic mm.\*
  • Women of child-bearing potential not willing to take contraception.
  • Patients with non-HCC malignancies within the past 5 years,excluding successfully treated squamous cell carcinoma and basal cell carcinoma of the skin.
  • Extrahepatic HCC tumor manifestation
  • Patients with a psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Patients under guardianship (e.g. individuals who are not able to freely give their informed consent).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Regensburg University

Regensburg, Bavaria, 93053, Germany

Location

Related Publications (5)

  • Schnitzbauer AA, Filmann N, Adam R, Bachellier P, Bechstein WO, Becker T, Bhoori S, Bilbao I, Brockmann J, Burra P, Chazoullieres O, Cillo U, Colledan M, Duvoux C, Ganten TM, Gugenheim J, Heise M, van Hoek B, Jamieson N, de Jong KP, Klein CG, Klempnauer J, Kneteman N, Lerut J, Makisalo H, Mazzaferro V, Mirza DF, Nadalin S, Neuhaus P, Pageaux GP, Pinna AD, Pirenne J, Pratschke J, Powel J, Rentsch M, Rizell M, Rossi G, Rostaing L, Roy A, Scholz T, Settmacher U, Soliman T, Strasser S, Soderdahl G, Troisi RI, Turrion VS, Schlitt HJ, Geissler EK. mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors. Ann Surg. 2020 Nov;272(5):855-862. doi: 10.1097/SLA.0000000000004280.

    PMID: 32889867DERIVED

  • Geissler EK, Schnitzbauer AA, Zulke C, Lamby PE, Proneth A, Duvoux C, Burra P, Jauch KW, Rentsch M, Ganten TM, Schmidt J, Settmacher U, Heise M, Rossi G, Cillo U, Kneteman N, Adam R, van Hoek B, Bachellier P, Wolf P, Rostaing L, Bechstein WO, Rizell M, Powell J, Hidalgo E, Gugenheim J, Wolters H, Brockmann J, Roy A, Mutzbauer I, Schlitt A, Beckebaum S, Graeb C, Nadalin S, Valente U, Turrion VS, Jamieson N, Scholz T, Colledan M, Fandrich F, Becker T, Soderdahl G, Chazouilleres O, Makisalo H, Pageaux GP, Steininger R, Soliman T, de Jong KP, Pirenne J, Margreiter R, Pratschke J, Pinna AD, Hauss J, Schreiber S, Strasser S, Klempnauer J, Troisi RI, Bhoori S, Lerut J, Bilbao I, Klein CG, Konigsrainer A, Mirza DF, Otto G, Mazzaferro V, Neuhaus P, Schlitt HJ. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Transplantation. 2016 Jan;100(1):116-25. doi: 10.1097/TP.0000000000000965.

    PMID: 26555945DERIVED

  • Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, Geissler EK. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma. BMC Cancer. 2010 May 11;10:190. doi: 10.1186/1471-2407-10-190.

    PMID: 20459775DERIVED

  • Geissler EK. Rapamycin enhances lifespan: at last, an advantage for transplant recipients? Nephrol Dial Transplant. 2009 Dec;24(12):3623-5. doi: 10.1093/ndt/gfp496. Epub 2009 Sep 22. No abstract available.

    PMID: 19773418DERIVED

  • Treiber G. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther. 2009 Feb;9(2):247-61. doi: 10.1586/14737140.9.2.247.

    PMID: 19192962DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cni protein, DrosophilaSteroidsCyclosporineTacrolimusAzathioprinePrednisoloneSirolimus

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring CompoundsPolycyclic CompoundsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsMacrolidesLactonesOrganic ChemicalsThionucleosidesSulfur CompoundsMercaptopurinePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesPregnadienetriolsPregnadienesPregnanes

Study Officials

  • Edward K Geissler, Prof. PhD

    Regensburg University Medical Center, Head of Experimental Surgery

    STUDY CHAIR

  • Hans J Schlitt, Prof. MD. FACS FRACS FRCS MHM

    Regensburg University Medical Center, Director of Surgical Department

    STUDY DIRECTOR

  • Andreas A Schnitzbauer, MD

    Regensburg University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

July 24, 2006

First Posted

July 25, 2006

Study Start

January 1, 2006

Primary Completion

April 1, 2009

Study Completion

May 1, 2014

Last Updated

July 30, 2014

Record last verified: 2009-07

Locations

DE(1)