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Sorafenib-tosylaat na een levertransplantatie bij de behandeling van patiënten met leverkanker

9 oktober 2026 bijgewerkt door: Jonsson Comprehensive Cancer Center

Een gerandomiseerde, multicenter, placebogecontroleerde, geblindeerde fase II-studie van adjuvante therapie met sorafenib bij ontvangers van een orthotope levertransplantatie (OLT) met een hoog risico met hepatocellulair carcinoom (HCC)

The purpose of this study is to determine if sorafenib (sorafenib tosylate) is a safe and effective treatment option for preventing liver cancer in high risk patients following liver transplantation. Liver transplantation is a treatment option for liver cancer patients, but despite transplantation, the liver cancer can recur in the new, transplanted liver. It is not known whether sorafenib is effective in preventing cancer recurrence in high risk patients following liver transplantation

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

PRIMARY OBJECTIVES:

I. Two-year recurrence free survival (RFS).

SECONDARY OBJECTIVES:

I. One-year recurrence free survival. II. Overall survival (OS). III. Safety. IV. Impact of drug-drug interactions (i.e. immunosuppression agents). V. Impact of biomarkers (alpha-fetoprotein [AFP], protein-induced by vitamin K absence or antagonist II [PIVKA II]).

VI. Effects of therapy on wound healing. VII. Impact of hepatitis C viral recurrence.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID).

ARM II: Patients receive placebo PO BID.

In both arms treatment continues for 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

73

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Alabama
      • Birmingham, Alabama, Verenigde Staten, 35294-0007
        • University of Alabama
    • California
      • Los Angeles, California, Verenigde Staten, 90095
        • Jonsson Comprehensive Cancer Center
    • Colorado
      • Denver, Colorado, Verenigde Staten, 80217-3364
        • University of Colorado
    • Connecticut
      • Hartford, Connecticut, Verenigde Staten, 06112
        • Mount Sinai Hospital
    • District of Columbia
      • Washington D.C., District of Columbia, Verenigde Staten, 20057
        • Lombardi Comprehensive Cancer Center at Georgetown University
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern University
    • Louisiana
      • New Orleans, Louisiana, Verenigde Staten, 70121
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, Verenigde Staten, 21287-8936
        • Johns Hopkins University
    • Massachusetts
      • Burlington, Massachusetts, Verenigde Staten, 01805
        • Lahey Clinic Medical Center
    • Michigan
      • Ann Arbor, Michigan, Verenigde Staten, 48109
        • University of Michigan University Hospital
    • Nebraska
      • Omaha, Nebraska, Verenigde Staten, 68198-7830
        • University of Nebraska Medical Center
    • New Jersey
      • Cherry Hill, New Jersey, Verenigde Staten, 08034
        • University of Pennsylvania Health System
    • New York
      • New York, New York, Verenigde Staten, 10016
        • New York University Langone Medical Center
      • New York, New York, Verenigde Staten, 10065
        • New York Presbyterian-The University Hospital of Columbia and Cornell
    • Ohio
      • Cleveland, Ohio, Verenigde Staten, 44195
        • Cleveland Clinic Foundation
    • Oklahoma
      • Oklahoma City, Oklahoma, Verenigde Staten, 73112
        • Integris-Baptist Medical
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Verenigde Staten, 15213
        • University of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, Verenigde Staten, 37232
        • Vanderbilt University
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • Baylor College of Medicine
      • Houston, Texas, Verenigde Staten, 77030
        • The Methodist Hospital Research Institute

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

19 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Patients must have hepatocellular carcinoma (HCC) with one of the following on explant: microvascular/macrovascular invasion, tumor outside of Milan criteria, poor tumor differentiation; patients with macrovascular invasion on explant pathology will be stratified

    * Additionally, the following will be included

    ** Patients with elevated surrogate markers (AFP > 500 or PIVKA > 400) pre transplant and with biopsy proven HCC prior to orthotopic liver transplantation (OLT) or on explant

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

  • Patients with a life expectancy > 12 weeks

  • Patients must have completed prednisone taper within 6 weeks post OLT

  • Patients must be enrolled between 6 to 12 weeks post OLT

  • Cadaveric donors only (no living donor liver transplantation [LDLT] or donor after cardiac death transplantation [DCDT])

  • No sorafenib prior to inclusion in the study

  • Platelet count > 50 x 10^9/L

  • Hemoglobin >= 8.5 g/dL

  • Total bilirubin =< 5 mg/dL

  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal

  • Amylase and lipase =< 1.5 x the upper limit of normal

  • Serum creatinine < 2 x the upper limit of normal

  • Prothrombin time (PT) =< 6 seconds or international normalized ratio (INR) =< 2.3

  • AFP > 500 (pre-transplant)

  • PIVKA > 400 (pre-transplant)

  • Patient has not received prior anti-angiogenic therapy, systemic targeted agents or systemic chemotherapy

    * Prior surgical resection, chemoembolization or other local therapy prior to transplant is permitted

  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test

  • Patients (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate

  • Patient must be able to swallow and retain oral medication

  • Patient must exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments

Exclusion Criteria:

  • Significant ongoing immunologic rejection based on pathology and clinical diagnosis (from time of transplant until randomization)

  • Use of T cell depleting agents for prevention or treatment of rejection at any point prior to or after enrollment in the study

  • Patient with documented evidence of metastatic disease

  • 100% tumor necrosis on explant pathology

  • Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression

  • Use of alemtuzumab

  • Living donor liver transplant (LDLT) or donation after cardiac death transplant (DCDT)

  • Human immunodeficiency virus (HIV) positive patients

  • Hepatitis C virus (HCV) recurrence at the time of randomization

  • Use of direct acting antivirals for HCV recurrence

  • Requirement of re-transplantation for primary non function

  • Uncontrolled hypertension, defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management

  • Active or clinically significant cardiac disease including:

    • Congestive heart failure - New York Heart Association (NYHA) > class II
    • Coronary artery disease
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
    • Unstable angina or new-onset angina within 3 months before randomization, or myocardial infarction (MI) within 6 months before randomization

  • Clinically active serious infection documented by positive cultures or an incomplete course of treatment for bacteremia or fungemia

  • Evidence or history of bleeding diathesis or coagulopathy

  • Patients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomization

  • Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks [TIAs]) within 6 months before randomization

  • Prior use of raf-kinase inhibitors (sorafenib), vascular endothelial growth factor (VEGF) inhibitors, mitogen-activated protein kinase (MAPK)/extracellular-signal-related kinase (ERK) kinase (MEK) inhibitors, or farnesyl transferase inhibitors

  • Patients using cytochrome P450 3A4 (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort dexamethasone) at a dose of greater than 16 mg daily, or rifampin and/or rifabutin within 28 days before randomization

  • Patients with non-HCC malignancy except those with DCIS (ductal carcinoma in situ), cervical cancer in-situ, basal cell or superficial bladder tumor; patients surviving a cancer that was curatively treated and without evidence of recurrence for more than 3 years before randomization are allowed

  • Presence of a non-healing wound, non-healing ulcer, or bone fracture

  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial

  • Any malabsorption condition

  • Women who are pregnant or breast-feeding

  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments

  • Patients with fibrolamellar HCC, cholangiocarcinoma, and combined HCC-cholangiocarcinoma

  • Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation

  • Prior use of any systemic chemotherapy for HCC

  • Prior use of systemic investigational agents for HCC

  • Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors

  • Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), will not be permitted within 3 weeks prior to study entry; G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the discretion of the investigator; however, they may not be administered to prevent a dose reduction; patients taking chronic erythropoietin are permitted, provided no dose adjustment is undertaken within 1 month prior to randomization or during the study

  • Autologous bone marrow transplant or stem cell rescue within four months of start of study drug

  • Concomitant treatment with rifampin and St. John's wort

  • Concomitant oral mTOR inhibitor treatment

  • Use of direct acting antivirals for HCV recurrence

  • Use of T-cell depleting agents

  • Use of alemtuzumab

  • Anticoagulation, as described below, is allowed:

    • Vitamin-K antagonists (e.g., warfarin)

      ** Low dose warfarin (1 mg orally, once daily) with PT-INR =< 1.5 x ULN is permitted; patients taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes

    • Low dose aspirin (=< 100 mg daily).

    • Heparins and heparinoids Use of any other investigational drug

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Enkel

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm I (sorafenib tosylate)

Patients receive sorafenib tosylate PO BID.
Ander: laboratory biomarker analysis

Correlative studies

Geneesmiddel: sorafenib tosylate

Given PO

Andere namen:
  • BAAI 43-9006
  • BAY 43-9006 Tosylaatzout
  • BAAI 54-9085
  • Nexavar
  • SFN
Placebo-vergelijker: Arm II (placebo)

Patients receive placebo PO BID.
Ander: laboratory biomarker analysis

Correlative studies

Ander: placebo

Given PO

Andere namen:
  • PLCB

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Recurrence-free Survival at 2 Years
Tijdsspanne: Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 2 years

Recurrence-free Survival at 2 Years: The number of participants who were alive without recurrence of hepatocellular carcinoma (HCC). Recurrence-free survival was defined as the time from randomization to the first documented HCC recurrence or death from any cause, whichever occurred first.
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 2 years

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Recurrence-free Survival at One Year
Tijdsspanne: Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 1 year

Recurrence-free Survival at One Year: The number of participants who were alive without recurrence of hepatocellular carcinoma (HCC). Recurrence-free survival was defined as the time from randomization to the first documented HCC recurrence or death from any cause, whichever occurred first.
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 1 year
Overall Survival
Tijdsspanne: From randomization through the last available follow-up, approximately two years

The number of participants who were alive at the last available follow-up. Overall survival was defined as the time from randomization to death from any cause or the last date the participant was known to be alive.
From randomization through the last available follow-up, approximately two years
Graft Failure Free Survival
Tijdsspanne: From randomization through the end of study follow-up, approximately two years

Graft Failure Free Survival: The number of participants who remained alive without failure of the transplanted liver. Graft-failure-free survival was defined as the time from randomization to the first documented graft failure according to local clinical standards.
From randomization through the end of study follow-up, approximately two years
Serum Alpha-fetoprotein (AFP) Correlation to Recurrence
Tijdsspanne: From randomization through the end of study follow-up, approximately two years

Serum Alpha-fetoprotein (AFP) Correlation to Recurrence: Among participants who experienced hepatocellular carcinoma (HCC) recurrence, this outcome assessed whether serum alpha-fetoprotein (AFP), a blood biomarker used to monitor HCC, was associated with recurrence.
From randomization through the end of study follow-up, approximately two years
Serum Alpha-fetoprotein (AFP) 24 Months
Tijdsspanne: Assessed at two years

Serum Alpha-fetoprotein (AFP) 24 Months: Serum alpha-fetoprotein (AFP), a blood biomarker used to monitor hepatocellular carcinoma (HCC), was measured during follow-up. Results are reported as the median AFP level at 24 months.
Assessed at two years
Adverse Events Assessed in Terms of Seriousness, Severity, and Relationship to the Study Material According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Tijdsspanne: Assessed from randomization through up to 30 days after last drug dose, approximately two years

See section four, Adverse events and serious adverse events
Assessed from randomization through up to 30 days after last drug dose, approximately two years
Impact of Sorafenib-Tacrolimus Interactions
Tijdsspanne: During the 24-month study treatment periodmeasured at 24 months

Median tacrolimus levels (ng/mL) measured at 24 months
During the 24-month study treatment periodmeasured at 24 months
Wound Complications
Tijdsspanne: During the 24-month study treatment period

Impact of therapy on wound healing
During the 24-month study treatment period
Hepatitis C Viral Recurrence
Tijdsspanne: During the 24-month study treatment period

data was insufficient to analyze the impact of Hepatitis C viral recurrence
During the 24-month study treatment period

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Jonsson Comprehensive Cancer Center

Medewerkers

Bayer

Onderzoekers

  • Hoofdonderzoeker: Fady Kaldas, MD, Jonsson Comprehensive Cancer Center

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

8 november 2012

Primaire voltooiing (Werkelijk)

1 februari 2023

Studie voltooiing (Werkelijk)

1 februari 2023

Studieregistratiedata

Eerst ingediend

18 juni 2012

Eerst ingediend dat voldeed aan de QC-criteria

19 juni 2012

Eerst geplaatst (Geschat)

20 juni 2012

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 november 2026

Laatste update ingediend die voldeed aan QC-criteria

9 oktober 2026

Laatst geverifieerd

1 februari 2023

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 11-003311
  • NCI-2012-00911 (Register-ID: CTRP (Clinical Trial Reporting Program))

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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