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Adult Primary Hepatocellular CarcinomaPhase 2NCT01624285

Sorafenib Tosylate Following a Liver Transplant in Treating Patients With Liver Cancer

A Phase 2 study testing sorafenib tosylate and laboratory biomarker analysis in people with Adult Primary Hepatocellular Carcinoma and Localized Resectable Adult Primary Liver Cancer, run by Jonsson Comprehensive Cancer Center at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
sorafenib tosylate and laboratory biomarker analysis
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
73 participants
Where
21 sitesUnited States
Study dates
8 Nov 2012to Feb 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • University of Michigan University Hospital

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • University of Alabama

    Birmingham, Alabama, 35294-0007

  • Lahey Clinic Medical Center

    Burlington, Massachusetts, 01805

  • University of Pennsylvania Health System

    Cherry Hill, New Jersey, 08034

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Colorado

    Denver, Colorado, 80217-3364

  • Mount Sinai Hospital

    Hartford, Connecticut, 06112

  • Baylor College of Medicine

    Houston, Texas, 77030

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

  • Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • New York University Langone Medical Center

    New York, New York, 10016

  • New York Presbyterian-The University Hospital of Columbia and Cornell

    New York, New York, 10065

  • Integris-Baptist Medical

    Oklahoma City, Oklahoma, 73112

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-7830

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Lombardi Comprehensive Cancer Center at Georgetown University

    Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

Official title: A Phase II Randomized Multicenter Placebo-Controlled Blinded Study of Sorafenib Adjuvant Therapy in High Risk Orthotopic Liver Transplant (OLT) Recipients With Hepatocellular Carcinoma (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

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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.

Being tested
sorafenib tosylate, placebo, laboratory biomarker analysis
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given PO

  • placeboOther

    Also called PLCB

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01624285
Study groupRoleWhat they receive
Arm I (sorafenib tosylate)ExperimentalPatients receive sorafenib tosylate PO BID.
Receives: Drug: sorafenib tosylate; Other: laboratory biomarker analysis
Arm II (placebo)Placebo comparatorPatients receive placebo PO BID.
Receives: Other: placebo; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrence-free Survival 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.

    Measured: 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

Secondary outcomes (9)

  1. Recurrence-free Survival at One 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.

    Measured: 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

  2. Overall Survival

    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.

    Measured: From randomization through the last available follow-up, approximately two years

  3. Graft Failure Free Survival

    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.

    Measured: From randomization through the end of study follow-up, approximately two years

  4. Serum Alpha-fetoprotein (AFP) Correlation to Recurrence

    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.

    Measured: From randomization through the end of study follow-up, approximately two years

  5. Serum Alpha-fetoprotein (AFP) 24 Months

    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.

    Measured: Assessed at two years

  6. 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

    See section four, Adverse events and serious adverse events

    Measured: Assessed from randomization through up to 30 days after last drug dose, approximately two years

  7. Impact of Sorafenib-Tacrolimus Interactions

    Median tacrolimus levels (ng/mL) measured at 24 months

    Measured: During the 24-month study treatment periodmeasured at 24 months

  8. Wound Complications

    Impact of therapy on wound healing

    Measured: During the 24-month study treatment period

  9. Hepatitis C Viral Recurrence

    data was insufficient to analyze the impact of Hepatitis C viral recurrence

    Measured: During the 24-month study treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2012 (estimated)
  2. Study start8 Nov 2012
  3. Primary completionFeb 2023
  4. Study completionFeb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01624285
Sponsor's protocol ID
11-003311
Other IDs
NCI-2012-00911
Status last verified
Feb 2023
First submitted
18 Jun 2012
Last updated
3 Nov 2026
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sorafenib tosylate and laboratory biomarker analysis in people with Adult Primary Hepatocellular Carcinoma and Localized Resectable Adult Primary Liver Cancer, run by Jonsson Comprehensive Cancer Center at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free Survival at 2 Years (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01624285.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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