Sunitinib and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Intervention: doxorubicin hydrochloride; sunitinib malate; laboratory biomarker analysis; hepatic artery embolization; quality-of-life assessment
Intervention description: Transarterial chemoembolization; Given Orally; Correlative Study; Surgical procedure; Correlative Study
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult primary hepatocellular carcinoma; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer

Summary:

      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.
    

Eligibility 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