Inability to recruit and adequate number of participants

This open-label study will pilot the use of systemic sunitinib malate, a dual inhibitor of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), in five participants with Von Hippel-Lindau (VHL) to investigate its potential efficacy as a treatment for retinal angiomas. Participants will have visual dysfunction with either visual acuity loss or visual field loss from retinal angiomas secondary to genetically confirmed VHL. This open-label study will pilot the use of systemic sunitinib malate in five participants to investigate its potential efficacy as a treatment for retinal angiomas associated with VHL. Participants will receive nine months of sunitinib malate therapy (six cycles total - one cycle consists of 50 mg oral dose once daily for four weeks followed by a two week rest period). The primary outcome will be a change in the best-corrected visual acuity of more than or equal to 15 letters from baseline to the Week 36 visit. The secondary ocular outcomes will focus on retinal thickness and leakage of the retinal angioma at the Week 36 visit. Optical coherence tomography will document changes in retinal thickening and fluorescein angiography will be used to determine leakage of the retinal angioma.

Inclusion Criteria

1. Participant must understand and sign the informed consent.
2. Participant must be at least 18 years of age.
3. Participant must have genetically confirmed VHL disease.
4. Participant must have an optic nerve angioma secondary to VHL in one or both eyes.
5. 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.
6. Participant must have clear ocular media and adequate pupillary dilation to permit good quality stereoscopic fundus photography.
7. All women of childbearing potential must have a negative urine pregnancy test at baseline, and have regular 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).
8. 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.
9. Participants must have normal organ and marrow function as defined below: WBC count ≥ 3,000/µL, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 100,000/µL, HGB> 10g/dl, serum creatinine ≤ 2.0 or measured 24 hr. creatinine clearance > 50 ml/min, AST and ALT < 2.5 x ULN, total bilirubin ≤ ULN (< 3 x NL in participants with Gilbert's disease).
10. Participant must have a negative HbsAg and nonreactive HCV.
11. 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.
12. Participant must be at least four weeks from completion of any investigational therapy for VHL.
13. Participant must have an ECOG performance score of 0-2. (See Appendix 3 - ECOG Performance Criteria).
14. Participant has recovered from the acute toxicities of prior treatment for VHL.

Exclusion Criteria

1. Participant has a history (within past five 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.
2. Participant has a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation, ≥ three beats in a row) or left ventricular ejection fraction ≤ 40%.
3. Participant has a history of serious intercurrent medical illness.
4. Participant had transient ischemic attacks or cerebrovascular accident within 12 months of study entry.
5. Participant has hypertension that cannot be controlled with medications (persistent elevation of systolic BP > 150 or diastolic BP > 100 mmHg despite optimal medical therapy).
6. Participant is on therapeutic anticoagulation, including aspirin.
7. 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.
8. Participant has received any major surgical procedures within one month of study entry or has surgical scars that have not healed.
9. Participant has a known serious allergy to fluorescein dye.
10. 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).
11. 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.
12. Participant has had chemotherapy or radiotherapy within four weeks (six 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 four weeks earlier.
13. Participant is receiving other investigational agents.
14. Participants with known brain metastases (except when adequately controlled, i.e., have not grown in size, for ≥ 6 months before enrollment), not including hemangioblastoma, a known VHL complication of the brain.
15. Participant has a known bleeding disorder.
16. Participant is currently taking sunitinib malate or has taken sunitinib malate in the past.

Early termination of the trial resulted in a small number of participants being analyzed, and Microperimetry (MP-1) results were not accurate for either participant due to fixation issues.