Sunitinib Malate (SUO11248) In Subjects W/ Metastatic And/Or Surgically Unresectable Hepatocellular Cancers (HCC)
Condition: Liver Cancer
MeSH terms: Liver Neoplasms; Carcinoma, Hepatocellular
Intervention: Sunitinib Malate
Intervention description: Once daily oral doses on days 1-28 of each 42-day cycle. The dose for the first 2 cycles will be 37.5 mg daily for 28 days, every 42 days. Dose may be escalated to 50 mg daily for 28 days at the treating investigator's discretion.
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatocellular cancer (HCC); Sunitinib malate; Vascular endothelial growth factor (VEGF); Platelet-derived growth factor (PDGF); Tyrosine kinases; Liver

Summary:

      An open label multi-site phase II clinical trial of dose escalated sunitinib malate given
      orally once daily on days 1-28 of each 42-day cycle. Treatment will be continued until there
      is either disease progression or cumulative or acute toxicity which in the opinion of the
      treating physician compromises the ability of the patient to receive treatment or patient
      desire to stop treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or
             surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for
             Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1.

          -  Adequate organ function as defined by the following criteria:

               -  Serum aspartate transaminase (AST); serum glutamic oxaloacetic transaminase
                  (SGOT) and serum alanine transaminase (ALT); serum glutamic pyruvic transaminase
                  (SGPT) less than or equal to 2.5 x local laboratory upper limit of normal (ULN),
                  or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are
                  due to underlying malignancy

               -  Total serum bilirubin less than or equal to 1.5 x ULN

               -  Absolute neutrophil count (ANC) more than or equal to 1500/mcL

               -  Platelets more than or equal to 100,000/mcL

               -  Hemoglobin more than or equal to 9.0 g/dL

               -  Serum calcium less than or equal to 12.0 mg/dL

               -  Serum creatinine less than or equal to 1.5 x ULN

          -  Biopsy-proven disease

          -  Measurable disease radiographically

          -  Disease that is deemed surgically unresectable (awaiting orthotopic hepatic
             transplantation allowable) and/or metastatic

          -  Age greater or equal to 18 years

          -  Life expectancy greater than 16 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky
             score > 60%)

        Exclusion Criteria:

          -  Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the
             study treatment

          -  NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment

          -  History of or known brain metastases, spinal cord compression, or carcinomatous
             meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening
             computed tomography (CT) or magnetic resonance imaging (MRI) scan

          -  Any of the following within the 6 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack, or pulmonary embolism.

          -  Known brain metastases

          -  Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2

          -  Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2, atrial
             fibrillation of any grade, or prolongation of the QTc interval to > 450msec for males
             or > 470 msec for females

          -  Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
             medical therapy)

          -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range with medication

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness or other active infection

          -  Concurrent treatment on another clinical trial; supportive care trials or
             non-treatment trials, e.g. Quality of Life (QOL), are allowed

          -  Concomitant use of ketoconazole or other agents known to induce CYP3A4

          -  Concomitant use of theophylline and phenobarbital and/or other agents metabolized by
             the cytochrome P450 system

          -  Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po
             daily for thrombo prophylaxis is allowed)

          -  Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy. All female subjects with reproductive potential must have a negative
             pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically
             sterile or must agree to use effective contraception during the period of therapy. The
             definition of effective contraception will be based on the judgment of the principal
             investigator or a designated associate.

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.