Chemoembolization of the Liver With or Without Sunitinib Malate in Treating Patients With Liver Cancer

OBJECTIVES:

Primary

• To evaluate unacceptable bleeding or hepatic failure at 10 weeks post-treatment in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization in combination with sunitinib malate versus transarterial chemoembolization alone.
• To evaluate the overall survival of these patients.

Secondary

• To evaluate the tumor stabilization rate in these patients.
• To evaluate the safety of this regimen in these patients.
• To evaluate the disease-free survival of these patients.
• To evaluate the relapse-free survival of these patients.
• To evaluate the quality of life of these patients.
• To evaluate the overall survival rate at 2 years of these patients.

OUTLINE: This is a multicenter study.

Pilot: Patients receive oral sunitinib malate once daily on days 1-28. Beginning 7-10 days later, patients undergo 1-3 courses of transarterial chemoembolization (TACE). Treatment repeats every 6 weeks for 1 year.

Randomization: Patients are stratified according to main tumor diameter (< 5 cm vs ≥ 5 cm), nodular involvement (uninodular vs multinodular), and center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive sunitinib malate and TACE as in the pilot phase.
• Arm II: Patients receive oral placebo once daily on days 1-28 and TACE as in the pilot phase.

Quality of life is assessed periodically.

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatocellular carcinoma or liver tumor responding to the Barcelona criteria
• Child-Pugh score of 5-6 (Class A)
• Tumor suitable for transarterial chemoembolization (one or more planned courses allowed)
• Tumor not suitable for surgical resection
• No extrahepatic metastases, including cerebral metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Hemoglobin ≥ 10 g/dL
• PT ≥ 50%
• Creatinine ≤ 120 μmol/L
• Bilirubin normal
• ALT/AST ≤ 3.5 times upper limit of normal (ULN)
• Alkaline phosphatases ≤ 4 times ULN
• Fibrinogen ≥ 1.5 g/L
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No portal vein thrombosis
• Able to comply with scheduled follow-up and management of toxicity
• No uncontrolled hypertension or requiring ≥ 2 classes of antihypertensive drugs
• No concomitant disease or uncontrolled severe disease
• No contraindications to the vascular occlusion procedure
• No prior or concurrent malignancy within the past 5 years, except adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin
• No psychiatric disability or social, family, or geographic reason for which the patient may not be followed regularly

PRIOR CONCURRENT THERAPY:

• At least 7 days since prior CYP3A4 inhibitors or inducers
• At least 3 months since prior radiofrequency ablation
• No prior chemotherapy
• No prior sunitinib, sorafenib, or any other inhibitors of angiogenesis
• No concurrent participation in another trial