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A Phase II Study of SUNITINIB MALATE (Sutent) and Chemoembolization in Patients With Unresectable Hepatocellular Cancer

Phase 2
18 Years
Open (Enrolling)
Liver Cancer

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Trial Information

A Phase II Study of SUNITINIB MALATE (Sutent) and Chemoembolization in Patients With Unresectable Hepatocellular Cancer



- To determine the response rate (complete, partial, and minimal response) in patients
with unresectable hepatocellular carcinoma treated with sunitinib malate in combination
with transarterial chemoembolization (TACE).

- To determine the progression-free survival at 4 months of patients treated with this


- To determine overall survival of these patients.

- To determine if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be
used to measure decrease in tumor perfusion and vascular permeability as a result of
treatment with sunitinib malate in combination with TACE, and if it can be useful in

- To examine the safety and tolerability of this regimen.

- To determine if a change in circulating endothelial precursor cell number and total
monocyte count on days 3, 8, 10, and 35 of therapy (as compared with levels at
baseline) and decrease in soluble vascular endothelial growth factor receptor-2 in
serum on days 8 (before TACE), 10, and 35 of therapy (as compared with baseline)
correlate with improved response and survival.

- To determine the effect of this therapy on quality of life as measured by the FACT-HEP
scale prior to each course of therapy.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on
days 1-28 in all subsequent courses. Patients undergo hepatic artery chemoembolization with
doxorubicin hydrochloride on day 8 of course 1 only. Treatment with sunitinib malate repeats
every 6 weeks* in the absence of disease progression or unacceptable toxicity.

NOTE: *Course 1 is 7 weeks in duration; all subsequent courses are 6 weeks in duration.

Blood samples are collected at baseline and periodically during study to measure circulating
endothelial precursor cell levels, total monocyte count, and soluble vascular endothelial
growth factor receptor-2.

Quality of life is assessed by the FACT-HEP scale at baseline, prior to each course of
treatment, and then at the completion of treatment.

After completion of study treatment, patients are followed every 6 months.

Inclusion Criteria


- Histologically, cytologically, or serologically* confirmed hepatocellular carcinoma
meeting the following criteria:

- 1-4 lesions

- Involvement of 1 or both liver lobes NOTE: *Alpha-fetoprotein (AFP) > 500 mcg/L
in high-risk patients

- Measurable disease by CT scan or MRI

- Disease does not exceed 50% of the liver parenchyma

- At least 1 lesion ≥ 3 cm in longest diameter

- Tumor burden involves < 50% of the liver

- Refused surgery OR unresectable disease due to any of the following:

- Multifocality

- Advanced cirrhosis

- Comorbid illness

- Candidate for chemoembolization

- No fibrolamellar histology

- No ascites

- No known brain metastases


- ECOG performance status 0-2

- Life expectancy ≥ 12 weeks

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Hemoglobin ≥ 8.5 g/dL (transfusion allowed)

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 2 mg/dL

- AST ≤ 5 times upper limit of normal (ULN)

- INR < 1.5

- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min

- No bleeding diathesis or coagulopathy

- No active congestive heart failure

- No uncontrolled angina

- No myocardial infarction within the past 12 months

- No cardiac arrhythmia

- Ejection fraction ≥ 45% (in patients with known coronary artery disease and in
patients > 50 years of age)

- Child-Pugh class A or B cirrhosis

- No impedance of hepatopedal blood flow (portal vein thrombosis)

- No thrombosis of the main portal vein

- No encephalopathy

- No biliary obstruction

- No variceal bleed within the past 6 months

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to sunitinib malate

- No absolute contraindication to doxorubicin, iodinated contrast material,
microfibrillar collage hemostat, or dexamethasone

- No other concurrent uncontrolled illness including, but not limited to, any of the

- Ongoing or active infection

- Psychiatric illness or social situation that would limit compliance with study

- No other active malignancies within the past year except nonmelanoma skin cancer or
carcinoma in situ

- No significant traumatic injury within the past 4 weeks

- No QTc prolongation (i.e., QTc interval ≥ 500 msec) or other significant ECG

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after the
completion of study treatment


- Recovered from prior therapy

- Prior liver-directed therapy, such as chemoembolization, radiofrequency ablation,
cryoablation, or ethanol injection allowed if the following criteria are met:

- Treated lesion remains inactive by CT scan or MRI and new lesion being embolized
is distinct from the previously treated lesion

- Radiographic progression of previously treated lesion requiring re-embolization

- Prior liver resection allowed

- Prior immunotherapy allowed

- No prior antiangiogenesis therapy

- No prior liver transplantation

- Patients awaiting a cadaveric or orthotopic liver transplantation are eligible
provided they have end-stage liver disease with a priority score of < 20 points

- More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- More than 4 weeks since prior major surgery or open biopsy

- At least 1 week since prior fine needle biopsy

- No concurrent immunotherapy

- No concurrent radiotherapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g.,

- Doses of ≤ 1 mg/day are allowed for prophylaxis of thrombosis as long as INR ≤

- Both full dose and prophylactic dose low molecular weight heparin allowed as
long as PT INR ≤ 1.5

- No anticipated major surgery during and for 3 months after completion of study

- No other concurrent investigational agents

- No other concurrent anticancer therapy

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate as measured by dynamic contrast-enhanced (DCE) CT scans

Outcome Time Frame:

Baseline, day 8, day 10, day28, day 35

Safety Issue:


Principal Investigator

Renuka Iyer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

April 2007

Completion Date:

Related Keywords:

  • Liver Cancer
  • adult primary hepatocellular carcinoma
  • advanced adult primary liver cancer
  • localized unresectable adult primary liver cancer
  • recurrent adult primary liver cancer
  • Liver Neoplasms



Roswell Park Cancer Institute Buffalo, New York  14263