Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00844168
Recruitment Status : Completed
First Posted : February 16, 2009
Last Update Posted : March 27, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

February 13, 2009
February 16, 2009
March 27, 2015
January 2009
June 2010   (Final data collection date for primary outcome measure)
Dose-limiting toxicity (DLT) as defined by the Common Terminology for Adverse Events (CTAE) version 3 [ Time Frame: 28 days ]
Defined as grade >= 3 nonhematologic/hematologic toxicity
  • Safety
  • Toxicity profile as assessed by NCI CTCAE v3.0
Complete list of historical versions of study NCT00844168 on Archive Site
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Explant and allograft expression of VEGF, PDGFR, CD34 (microvessel density), and Ki67 (proliferation marker)
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Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant
Phase I Adjuvant Trial of Sorafenib in Hepatocellular Carcinoma Patients After Liver Transplantation
This phase I trial studies the side effects and best dose of sorafenib tosylate in treating patients with liver cancer who have undergone a liver transplant. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib after liver transplant may be an effective treatment for liver cancer


I. Establish the safety and toxicity profile of sorafenib administered daily to hepatocellular carcinoma (HCC) patients who have undergone orthotopic liver transplantation.


I. Determine explant and allograft expression of vascular endothelial growth factor (VEGF), platelet derived growth factor receptor (PDGFR), microvessel density (CD34) and Ki67 (proliferation marker).

OUTLINE: Patients receive sorafenib tosylate orally (PO) twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adult Primary Hepatocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Localized Resectable Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Drug: sorafenib tosylate
    Given orally
    Other Names:
    • BAY 43-9006
    • BAY 43-9006 Tosylate Salt
    • BAY 54-9085
    • Nexavar
    • SFN
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (adjuvant sorafenib tosylate after liver transplant)
Patients receive sorafenib tosylate PO twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Drug: sorafenib tosylate
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
June 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with HCC on explant, who have not received prior systemic anti-cancer treatment for HCC
  • HCC patients who have undergone orthotopic liver transplantation, are at high risk for tumor recurrence or who have high suspicion or documentation of tumor recurrence
  • Patients who have a life expectancy of at least 12 weeks
  • Patients must have one of the following disease states:

    • Patients are 4 weeks beyond and less than 60 days from liver transplant surgery (to first study treatment) who have no residual hepatocellular carcinoma following liver transplantation;
    • Patients with post transplant recurrent hepatocellular carcinoma within the liver or at an extra hepatic site, diagnosed by radiographic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) consistent with hepatocellular carcinoma or proved by biopsy, within 24 months of transplantation;
    • Post-transplant patients with rising alpha-feta protein level > 500ng/mL, even in the absence of confirmed disease within 24 months of transplant
  • Patients must have one of the following explant histological features of HCC:bilobar tumor; macrovascular invasion; or multifocality; if patients have well-differentiated HCC, they must have all three features
  • Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Platelet count >= 60 x 10^9/L
  • Hemoglobin >= 8.5 g/dL
  • Total bilirubin =< 3 mg/dL
  • Alanine transaminase (ALT) and aspartate transaminase (AST) =< 5 x upper limit of normal
  • Amylase and lipase =< 1.5 x the upper limit of normal
  • Serum creatinine =< 1.5 x the upper limit of normal
  • Prothrombin time (PT)-international normalized ratio (INR) =< 2.3 or PT 6seconds above control
  • Patients who give written informed consent

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma,superficial bladder tumors (Ta, Tis & T1); any cancer curatively treated > 3 years prior to entry is permitted
  • Renal failure requiring hemo- or peritoneal dialysis
  • History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers ordigoxin; or uncontrolled hypertension; myocardial infarction more than 6months prior to study entry is permitted
  • Active clinically serious infections > grade 2 (National Cancer Institute -Common Terminology Criteria for Adverse Events version 3.0)
  • Known history of human immunodeficiency virus (HIV) infection
  • Known central nervous system tumors including metastatic brain disease
  • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial
  • Patients unable to swallow oral medications
  • 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; women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug; both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial
  • Prior use of any systemic anti-cancer chemotherapy for HCC
  • Prior use of systemic investigational agents for HCC
  • Prior use of Raf-kinase inhibitors (RKI), VEGF inhibitors, MEK inhibitors or Farnesyl transferase inhibitors
  • Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), 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 substituted for a required dose reduction)
  • Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 1 month prior to the study 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 anti-coagulation therapy with warfarin
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
NCI-2009-01659 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Not Provided
Not Provided
University of Washington
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Edward Lin Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
University of Washington
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP