Know Cancer

or
forgot password

A Phase IB Study of Sorafenib for Patient With Locally Advanced or Metastatic Hepatocellular Carcinoma and Child's B Cirrhosis


Phase 1
18 Years
N/A
Not Enrolling
Both
Liver Cancer

Thank you

Trial Information

A Phase IB Study of Sorafenib for Patient With Locally Advanced or Metastatic Hepatocellular Carcinoma and Child's B Cirrhosis


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

4 years

Safety Issue:

No

Principal Investigator

Bert H. O'Neil, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC 0717

NCT ID:

NCT00767468

Start Date:

October 2008

Completion Date:

November 2010

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • advanced adult primary liver cancer
  • localized unresectable adult primary liver cancer
  • recurrent adult primary liver cancer
  • Fibrosis
  • Liver Neoplasms
  • Carcinoma, Hepatocellular

Name

Location

Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570