INCLUSION CRITERIA:
-Participant must understand and sign the informed consent.
-Participant must be at least 18 years of age.
-Participant must have genetically confirmed VHL disease.
-Participant must have an optic nerve angioma secondary to VHL in one or both eyes.
-Participant must have an optic nerve tumor that has caused any visual field depression on microperimetry-1 that correlates with the retinal angioma OR the participant clinically may have hard exudates correlating with the retinal angioma OR has best-corrected visual acuity of 20/40 or worse in the study eye.
-Participant must have clear ocular media and adequate pupillary dilation to permit good quality stereoscopic fundus photography.
-All women of childbearing potential must have a negative urine pregnancy test at baseline, and have monthly negative pregnancy testing while taking sunitinib malate. (Sunitinib malate has the potential for teratogenic or abortifacient effects, and no data regarding its safety in pregnant women are available).
-All women of childbearing potential who are sexually active and all men who are sexually active are required to use two forms of birth control during the course of the study.
-Participants must have normal organ and marrow function as defined below: WBC count greater than or equal to 3,000/microL, absolute neutrophil count greater than or equal to 1,500/microL, platelet count greater than or equal to 100,000/microL, HGB greater than 10g/dl, serum creatinine less than or equal to 2.0 or measured 24 hr. creatinine clearance greater than 50 ml/min, AST and ALT less than 2.5 x ULN, total bilirubin less than or equal to ULN (less than 3 x NL in participants with Gilbert's disease).
-Participant must have a negative HbsAg, HIV-1 and nonreactive HCV.
-Participant must have a negative HIV-1, as potential pharmacokinetic interactions of drugs used to treat HIV, such as anti-retroviral drugs, with sunitinib malate are unknown.
-Participant must be at least four weeks from completion of any investigational therapy for VHL.
-Participant must have an ECOG performance score of 0-2. (See Appendix 3 - ECOG Performance Criteria).
-Participant has recovered from the acute toxicities of prior treatment for VHL.
EXCLUSION CRITERIA:
-Participant has a history (within past 5 years) or evidence of severe cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, uncontrolled dysrhythmias, dysrhythmias requiring anti-arhythmic drugs, or has active ischemic heart disease including myocardial infarction and poorly controlled angina within 12 months of study entry.
-Participant has a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation, greater than or equal to 3 beats in a row) or left ventricular ejection fraction less than or equal to 40%.
-Participant has a history of serious intercurrent medical illness.
-Participants had transient ischemic attacks or cerebrovascular accident within 12 months of study entry.
-Participant has hypertension that cannot be controlled with medications (persistent elevation of systolic BP greater than 150 or diastolic BP greater than 100 mmHg despite optimal medical therapy).
-Participant is on therapeutic anticoagulation, including aspirin.
-Participant who is breast-feeding, as there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib malate.
-Participant has received any major surgical procedure within one month of study entry or has surgical scars that have not healed.
-Participant has a known serious allergy to fluorescein dye.
-Participant is currently taking drugs or ingesting food that affect sunitinib malate plasma concentrations: strong inhibitors of the CYP3A4 family (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) and/or inducers of the CYP3A4 family (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort).
-Participant has had a prior or concomitant non-VHL-associated malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin or any other malignancy from which the patient has remained disease free for more than five years.
-Participant has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (to grade 1 or less toxicity according to CTCAE 3.0) due to agents administered more than 4 weeks earlier.
-Participant is receiving other investigational agents.
-Participants with known brain metastases (except when adequately controlled, i.e., have not grown in size, for greater than or equal to 6 months before enrollment), not including hemangioblastoma, a known VHL complication of the brain.
-Participant has a known bleeding disorder.
-Participant is currently taking sunitinib malate or has taken sunitinb malate in the past.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/16/2008