Sunitinib and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

Roswell Park Comprehensive Cancer Center

Status and phase

Terminated

Phase 2

Conditions

Liver Cancer

Treatments

Procedure: quality-of-life assessment

Other: laboratory biomarker analysis

Drug: doxorubicin hydrochloride

Procedure: hepatic artery embolization

Drug: sunitinib malate

Study type

Interventional

Funder types

Other

Identifiers

NCT00524316

RPCI-I-82706

CDR0000563261

Details and patient eligibility

About

RATIONALE: Sunitinib 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. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Giving sunitinib together with chemoembolization may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sunitinib together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.

Full description

OBJECTIVES:

Primary

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

Secondary

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 prognosis.
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.

Enrollment

16 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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 following:
- Ongoing or active infection
- Psychiatric illness or social situation that would limit compliance with study requirements
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 abnormalities
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after the completion of study treatment

PRIOR CONCURRENT THERAPY:

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., warfarin)
- Doses of ≤ 1 mg/day are allowed for prophylaxis of thrombosis as long as INR ≤ 1.5
- 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 treatment
No other concurrent investigational agents
No other concurrent anticancer therapy