Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome

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Brief Title

Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome

Official Title

Pilot Study of Sunitinib Malate for Advanced Ocular Disease of Von Hippel-Lindau Syndrome

Brief Summary

      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.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36

Secondary Outcome

 Change in Retinal Thickness From Baseline to Week 36

Condition

Von Hippel-Lindau Syndrome

Intervention

Sunitinib Malate

Study Arms / Comparison Groups

 Sunitinib Malate
Description:  Participants were expected to receive 9 months of sunitinib malate therapy administered in 6 cycles. Each cycle consisted of a daily oral dose of 50 mg sunitinib malate for 4 weeks followed by a 2-week rest period).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

2

Start Date

May 2008

Completion Date

February 2011

Primary Completion Date

February 2011

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Catherine Meyerle, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00673816

Organization ID

080129

Secondary IDs

08-EI-0129

Responsible Party

Sponsor

Study Sponsor

National Eye Institute (NEI)


Study Sponsor

Catherine Meyerle, MD, Principal Investigator, NEI/NIH


Verification Date

November 2011