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Phase I Adjuvant Trial of Sorafenib in Hepatocellular Carcinoma Patients After Liver Transplantation

Phase 1
18 Years
Open (Enrolling)
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

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Trial Information

Phase I Adjuvant Trial of Sorafenib in Hepatocellular Carcinoma Patients After Liver Transplantation


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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity (DLT) as defined by the Common Terminology for Adverse Events (CTAE) version 3

Outcome Description:

Defined as grade >= 3 nonhematologic/hematologic toxicity

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Edward Lin

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109