Full Text View
Tabular View
No Study Results Posted
Related Studies
Sorafenib in Treating Patients With Locally Advanced or Metastatic Liver Cancer and Cirrhosis
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2009
First Received: October 4, 2008   Last Updated: April 23, 2009   History of Changes
Sponsors and Collaborators: UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00767468
  Purpose

RATIONALE: Sorafenib 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.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib in treating patients with locally advanced or metastatic liver cancer and cirrhosis.


Condition Intervention Phase
Liver Cancer
Drug: sorafenib tosylate
Other: pharmacological study
Radiation: Tc 99m sestamibi
Radiation: technetium Tc 99m mebrofenin
Phase I

MedlinePlus related topics: Cancer Cirrhosis Liver Cancer Radiation Therapy
Drug Information available for: Mebrofenin Technetium Tc 99m sestamibi Sorafenib Sorafenib tosylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase IB Study of Sorafenib for Patient With Locally Advanced or Metastatic Hepatocellular Carcinoma and Child's B Cirrhosis

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Correlation between hepatic retention and clearance of technetium Tc 99m mebrofenin (MEB) and technetium Tc 99m sestamibi (MIBI) and clearance (and other pharmacokinetic parameters) of sorafenib tosylate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerable dose of sorafenib tosylate [ Designated as safety issue: Yes ]
  • Correlation between the pharmacokinetics of MEB and MIBI and the dose-limiting toxicity of sorafenib tosylate [ Designated as safety issue: Yes ]
  • Conjugated or unconjugated bilirubin increase in response to sorafenib tosylate [ Designated as safety issue: No ]
  • Correlation between increased bilirubin and decreased clearance of MEB and/or MIBI [ Designated as safety issue: No ]
  • Correlation between survival and MRI characteristics associated with high tumor VEGF levels [ Designated as safety issue: No ]
  • Correlation between clearance of sorafenib tosylate and expression levels of hepatic transport proteins [ Designated as safety issue: No ]
  • Correlation between survival and activation of the RAF/MEK/ERK pathway at baseline [ Designated as safety issue: No ]
  • Median overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: October 2008
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the pharmacokinetic parameters of sorafenib tosylate in patients with locally advanced or metastatic hepatocellular carcinoma and Child-Pugh B cirrhosis.
  • To correlate the pharmacokinetic parameters of sorfenib tosylate with hepatic retention and clearance of technetium Tc 99m mebrofenin (MEB) and technetium Tc 99m sestamibi (MIBI).

Secondary

  • To establish a tolerable dose of sorafenib tosylate based on degree of liver dysfunction (bilirubin ≤ 3 times upper limit of normal [ULN] or bilirubin > 3 times but ≤ 6 times ULN).
  • To correlate the pharmacokinetics MEB and MIBI with the dose-limiting toxicity of sorafenib tosylate.
  • To explore whether increase in bilirubin consists primarily of conjugated or unconjugated bilirubin in response to sorafenib tosylate.
  • To explore whether there is a correlation between increased bilirubin and decreased clearance of MEB and/or MIBI.
  • To explore whether there is a correlation between survival and MRI characteristics associated with high tumor VEGF levels.
  • To assess VEGF levels directly in available biopsy samples using IHC.
  • To determine expression levels of hepatic transport proteins (i.e., OATPs, Pgp, or MRPs) that may correlate with clearance of sorafenib tosylate.
  • To explore whether there is a correlation between survival and activation of the RAF/MEK/ERK pathway at baseline.
  • To estimate median overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to degree of hepatic dysfunction (moderate [bilirubin ≤ 3 times upper limit of normal (ULN)] vs severe [bilirubin > 3 times but ≤ 6 times ULN]).

Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo hepatic scintigraphy with technetium Tc 99m mebrofinin (MEB) and technetium Tc 99m sestamibi (MIBI) at baseline. Blood and urine samples are collected periodically for pharmacokinetic studies.

After completion of study therapy, patients are followed at 3-4 weeks and then every 3 months thereafter.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of hepatocellular carcinoma (HCC) according to tissue histology* NOTE: *Recurrence of previously resected HCC does not require tissue confirmation if there is clear radiographic recurrence, in the opinion of the investigator
  • Locally advanced or metastatic disease OR not eligible for surgical resection or immediate liver transplantation
  • Child-Pugh class B cirrhosis

    • Moderate hepatic dysfunction (bilirubin ≤ 3 times upper limit of normal [ULN]) OR severe hepatic dysfunction (bilirubin > 3 times but ≤ 6 times ULN)
  • No known brain metastasis unless the metastasis has been stable for > 3 months

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 12 weeks
  • Hemoglobin > 9.0 g/dL
  • ANC > 1,000/mm^3
  • Platelet count > 45,000/mm^3
  • ALT and AST < 7 times ULN
  • INR < 2.0
  • Creatinine < 1.7 times ULN OR creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study treatment
  • No history of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, is clinically significant, precludes giving informed consent, or interferes with compliance of oral drug intake
  • No other concurrent active malignancy
  • No active clinically serious infection > CTCAE grade 2
  • No known hypersensitivity to sorafenib tosylate or to any of the excipients
  • No known or suspected allergy to sorafenib tosylate or to any agent given in the course of this study
  • No NYHA class III or IV congestive heart failure
  • No unstable angina
  • No new onset angina (i.e., within the past 3 months)
  • No myocardial infarction within the past 6 months
  • No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
  • No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
  • No pulmonary hemorrhage/bleeding event > CTCAE grade 2 within the past 4 weeks
  • No other hemorrhage/bleeding event > CTCAE grade 3 within the past 4 weeks
  • No variceal bleeding within the past 90 days
  • No known grade 2 or 3 esophageal varices
  • No evidence or history of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 4 weeks
  • No serious non-healing wound, ulcer, or bone fracture
  • No other serious uncontrolled medical condition (e.g., uncontrolled ascites or encephalopathy) that, in the opinion of the investigator, may compromise study participation
  • No condition that would impair the patient's ability to swallow whole pills
  • No malabsorption problem
  • No active drug or alcohol abuse

PRIOR CONCURRENT THERAPY:

  • No more than one prior therapy including, but not limited to, any of the following:

    • Systemic chemotherapy
    • Hepatic artery infusion of chemotherapy
    • Chemoembolization
    • Radioembolization
    • Ablation
  • At least 4 weeks since prior embolization, resection, or ablation
  • No prior RAF/MEK/ERK-targeting therapy or VEGF-targeting therapy
  • More than 4 weeks since prior participation in an investigational drug study
  • More than 4 weeks since prior major surgery or open biopsy
  • No concurrent chronic anticoagulation other than 1 mg of warfarin per day for central venous catheter patency
  • No concurrent St. John's wort or rifampin
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00767468

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office - Lineberger Comprehensive Cancer Cente     877-668-0683; 919-966-4432        
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Bert H. O'Neil, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000615311, UNC-LCCC-0717, BAYER-UNC-LCCC-0717
Study First Received: October 4, 2008
Last Updated: April 23, 2009
ClinicalTrials.gov Identifier: NCT00767468     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer

Study placed in the following topic categories:
Liver Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Fibrosis
Liver Cirrhosis
Protein Kinase Inhibitors
Recurrence
Carcinoma
Liver Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Hepatocellular Carcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Liver Diseases
Neoplasms by Histologic Type
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Carcinoma, Hepatocellular
Fibrosis
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma
Liver Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Pathologic Processes
Therapeutic Uses
Adenocarcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009