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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00844168
First received: February 13, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
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
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Adjuvant Trial of Sorafenib in Hepatocellular Carcinoma Patients After Liver Transplantation

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Dose-limiting toxicity (DLT) as defined by the Common Terminology for Adverse Events (CTAE) version 3 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Defined as grade >= 3 nonhematologic/hematologic toxicity


Estimated Enrollment: 20
Study Start Date: January 2009
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00844168

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Edward Lin Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00844168     History of Changes
Other Study ID Numbers: 6697, NCI-2009-01659
Study First Received: February 13, 2009
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Liver Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014