Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization
Condition: Neuroendocrine Tumor; Islet Cell Tumor
MeSH terms: Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell
Intervention: Sunitinib malate; Hepatic Artery Embolizations
Intervention description: Sunitinib malate (Sutent) at a dose of 37.5mg will be administered orally once daily on days 1-28 in a 42-day cycle. Treatment with Sutent will begin no sooner than seven days after the first hepatic artery embolization. Subsequent embolizations (if necessary) will be scheduled during scheduled Sutent treatment breaks. No fewer than seven days shall separate treatment with Sutent and scheduling of hepatic artery embolizations.; 1-3 selective hepatic artery embolizations will be performed at approximately 5-week intervals, based on the extent of hepatic involvement with tumor.
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carcinoid; Pancreatic; Metastatic; Neuroendocrine; Tumors; Hepatic; Artery; Embolization; Angiogenesis; Sunitinib; Malate; Sutent; Tyrosine; Kinase; Inhibitor

Summary:

      The purpose of this study is to decide if a medicine that slows growth of new blood vessels
      can be give after the embolization procedure to prevent or delay new growth of blood vessels
      to tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Well-differentiated metastatic carcinoid tumors and pancreatic endocrine tumors with
             measurable liver metastases.

          -  Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or
             surgical procedures to National Cancer Institute Common Terminology Criteria for
             Adverse Events (NCI CTCAE) Version 3.0 grade less than or equal to 1.

          -  Adequate organ function as defined by the following criteria:

               1. 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

               2. Total serum bilirubin less than or equal to 1.5 x ULN

               3. Absolute neutrophil count (ANC) greater than or equal to 1500/microL

               4. Platelets greater than or equal to 100,000/microL

               5. Hemoglobin greater than or equal to 9.0 g/dL

               6. Serum calcium less than or equal to 12.0 mg/dL

               7. Serum creatinine less than or equal to 1.5 x ULN

               8. Prothrombin and activated partial thromboplastin time (PT and aPTT) less than or
                  equal to 1.5 x ULN

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2

          -  Informed Consent: Patients must be aware of the nature of his/her disease process and
             must willingly give consent after being informed of the experimental nature of
             therapy, alternatives, potential benefits, side-effects, risks and discomforts.

        Exclusion Criteria:

          -  Major surgery or radiation therapy within 4 weeks of starting the study treatment.

          -  Prior hepatic artery embolization or chemoembolization.

          -  Prior treatment with a tyrosine kinase inhibitor or a vascular endothelial growth
             factor (VEGF) inhibitor.

          -  NCI CTCAE 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.

          -  Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2.

          -  Prolonged corrected QT (QTc) interval on baseline electrocardiogram (EKG).

          -  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 and 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 by
             mouth (po) daily for thrombo prophylaxis is allowed).

          -  Pregnancy or breastfeeding. Female participants must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy. Female participants with reproductive potential must have a negative
             pregnancy test (serum or urine) prior to enrollment. Male participants must be
             surgically sterile or must agree to use effective contraception during the period of
             therapy.

          -  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 patient inappropriate for entry into
             this study.