Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow
Condition: Von Hippel-Lindau Syndrome; Renal Cell Carcinoma; Hemangioblastoma
MeSH terms: Carcinoma, Renal Cell; Hemangioblastoma; Von Hippel-Lindau Disease; Syndrome
Intervention: SU011248
Intervention description: 50 mg/day orally for 4 weeks, no treatment for 2 weeks (6 weeks = 1 cycle).
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: VHL Syndrome; Von Hippel-Lindau Syndrome; VHL Disease; Kidney; Retina; Brain; Spinal cord; Pancreas; Inner ear; Cysts; Tumors; Sunitinib Malate; SU011248; Sutent; VHL; Sunitinib; Renal cell carcinoma; Hemangioblastoma; Endothelium

Summary:

      The goal of this clinical research study is to learn if sunitinib malate (SU011248) can help
      to control VHL. The safety of this drug will also be studied.

      Primary objectives:

        -  Evaluate safety of treatment with SU011248/sunitinib malate (50 mg daily dose for 4
           weeks, then 2 weeks off) for 6 months in patients with Von Hippel-Lindau Syndrome (VHL)
           who have a measurable lesion undergoing surveillance

      Secondary objectives:

        -  Evaluate efficacy of treatment with SU011248/sunitinib malate (50 mg daily dose for 4
           weeks, then 2 weeks off) for 6 months in patients with VHL who have a measurable lesion
           undergoing surveillance

      Correlative objectives:

        -  Evaluate quality of life of SU011248/sunitinib malate therapy in VHL patients

        -  Evaluate peripheral blood lymphocyte receptor phosphorylation in VHL patients taking
           SU011248/sunitinib malate (optional procedure)

        -  Correlate results of dynamic contrast-enhanced and diffusion weighted MRI and dynamic
           contrast enhanced CT with response and explore findings suggestive of surrogates of
           early response (optional procedure)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have genetically confirmed Von Hippel-Lindau (VHL) disease.

          -  At least one measurable VHL-related lesion, which is undergoing surveillance, and
             patient is not at immediate risk of needing intervention for this or other lesions.
             Biopsy is not required given the known natural history in the setting of a positive
             genetic test. (1) Renal: solid mass suspicious for Renal Cell Carcinoma (RCC) >/= 1 cm
             or cystic mass >/= 1 cm; (2) Pancreas: Solid mass >/= 1cm & < 3cm suspicious for
             neuroendocrine tumor; (3) Brain: asymptomatic hemangioblastoma > 5mm; (4) Spine:
             asymptomatic hemangioblastoma, > 1cm; (5) Eye: asymptomatic peripapillary and/or
             macular hemangioblastoma, any size.

          -  Allowable prior therapy: (1) Patients having undergone prior therapy for VHL lesions
             may enroll as long as other criteria are met. Previously radiated lesions may not be
             considered as target lesions unless they demonstrate unequivocal evidence of growth;
             (2) Major surgery, chemotherapy or radiation therapy completed >4 weeks prior to
             starting the study treatment.

          -  Age >/= 18 years. Because no dosing or adverse event data are currently available on
             the use of SU011248/sunitinib malate in patients <18 years of age, children are
             excluded from this study but will be eligible for future pediatric single-agent
             trials, if applicable.

          -  Eastern Cooperative Oncology Group (ECOG) performance status </= 2

          -  Patients must have normal organ and marrow function as defined: (1) serum aspartate
             transaminase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine
             transaminase ([ALT]; serum glutamic pyruvic transaminase [SGPT]) </= 2.5 x local
             laboratory upper limit of normal (ULN), or AST and ALT</= 5 x ULN if liver function
             abnormalities are due to underlying malignancy; (2) Total serum bilirubin </=1.5 x
             ULN; (3) Absolute neutrophil count (ANC) >/= 1500mcL; (4) Platelets >/= 100,000 mcL;
             (5) Hemoglobin >/= 9.0 g/dL; (6) Serum creatinine < 1.5 x UL.

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of SU011248/sunitinib
             malate as listed below will be determined following review of their case by the
             Principal Investigators. If possible, efforts will be made to switch motivated
             patients to other medications, otherwise patients will be excluded: (1) Ketoconazole,
             (2) Theophylline, (3) Phenobarbital, (4) Coumadin at therapeutic doses (low dose
             Coumadin up to 2 mg po daily for thromboprophylaxis is allowed).

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Patients may not be receiving any other investigational agents.

          -  Patients with any metastatic disease of any kind.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to SU011248/sunitinib malate.

          -  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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
             Computer 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 >/= 2.

          -  Prolonged QTc interval on baseline electrocardiogram (ECG or EKG)>470ms.

          -  Hypertension that cannot be controlled by medications (>140/90 mm Hg despite optimal
             medical therapy).

          -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range with medication.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because SU011248/sunitinib malate has the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with SU011248/sunitinib malate, breastfeeding should be discontinued if the
             mother is treated with SU011248/sunitinib malate.

          -  Known HIV-positive patients taking combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with SU011248/sunitinib
             malate. Appropriate studies will be undertaken in patients receiving combination
             antiretroviral therapy when indicated.