Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma

August 29, 2019 updated by: Arman Mashayekhi
To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex) and compare it with safety and efficacy of intravitreal bevacizumab in eyes with macular edema after plaque radiotherapy of uveal melanoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Plaque radiotherapy is a commonly used method for treatment of small and medium-sized uveal melanomas. Macular edema is one of the most common causes of visual loss after plaque radiotherapy and has been reported in up to 70% of patients with posterior uveal melanoma. Different methods have been proposed for treatment of post-radiation macular edema and include periocular steroid, intravitreal steroid, intravitreal vascular endothelial growth factor (VEGF) inhibitors, photodynamic therapy, and macular laser photocoagulation.

Injection of intravitreal triamcinolone (a form of steroid) has been found to be useful for treatment of different forms of macular edema but is associated with considerable rates of increased intraocular pressure (glaucoma). Dexamethasone is more potent than triamcinolone and can be safely injected directly into the vitreous cavity (intravitreal injection) but unfortunately its use in the form of intravitreal injection is not practical due to the short half-life of intraocular dexamethasone (about 3 hours).

Within the past several years, tiny drug delivery systems have been developed that allow sustained release of minute amounts of steroid into the back part (vitreous cavity) of the eye, when they are implanted into the vitreous cavity. Ozurdex is a biodegradable dexamethasone intravitreal implant that has been shown to be well-tolerated and effective for up to 6 months in reducing vision loss and improving visual outcome in eyes with different types of macular edema including those secondary to diabetic retinopathy and retinal vein occlusion.

In this study the investigators would like to evaluate the safety and effectiveness of Ozurdex (dexamethasone intravitreal implant) for treatment of macular edema developing after plaque radiotherapy of uveal melanoma.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Ocular Oncology Service, Wills Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • Inclusion criteria:

    1. Patient age 18 years or more.
    2. Uveal melanoma treated with I-125 plaque radiotherapy.
    3. Visual acuity between 20/40 to 20/400 secondary to post-radiation macular edema.
    4. Central subfield retinal thickness > 300 micron.
    5. Duration of macular edema < 12 months.
    6. No potential contributing causes of decreased vision other than macular edema.

  • Exclusion criteria:

    1. Visual acuity worse than 20/400 or better than 20/40.
    2. Monocular patient or poor vision in the non-study eye (<20/80).
    3. History of vitrectomy surgery.
    4. Panretinal photocoagulation or intraocular surgery within 3 months of enrollment.
    5. Concomitant or previous radiation optic neuropathy.
    6. Use of periocular, intravitreal, or systemic steroids within 6 month of enrollment in the study eye.
    7. Use of intravitreal VEGF antagonist within 6 weeks of enrollment.
    8. History of ocular hypertension or glaucoma, or intraocular pressure (IOP)>21 mmHg.
    9. History of steroid-induced glaucoma in either eye.
    10. Active ocular infection or history of herpetic eye infection.
    11. Clinically significant epiretinal membrane in the study eye.
    12. Iris neovascularization in the study eye.
    13. Clinically significant media opacity preventing acquisition of good-quality optical coherence tomography (OCT) in the study eye.
    14. Aphakia or anterior chamber intraocular lens.
    15. Poorly controlled diabetes (Hemoglobin A1c level >13%).
    16. Poorly controlled hypertension (Systolic pressure > 160 mm Hg or diastolic pressure > 90 mm Hg).
    17. Pregnancy (women of childbearing age should have negative pregnancy test and use contraception).
    18. Presence of any ocular condition that in the opinion of one of the investigators will prevent at least 2 lines of improvement in best-corrected visual acuity.
    19. Interval between plaque radiotherapy for uveal melanoma and intended date of dexamethasone intravitreal implant of less than 6 months.
    20. Evidence of activity or inadequate regression of the treated uveal melanoma after plaque radiotherapy (based on the judgment of the study investigators).
    21. Known allergy or hypersensitivity to any of the study medications or their components.
    22. History of prior myocardial infarction or stroke.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ozurdex
Patients will be followed at 1 week after Ozurdex insertion (0.7 mg) and then at 1,2, 3,4, 5, and 6 months. Following the 6-month visit, patients will be seen every 2 months. At each visit patients will be checked for side effects of treatment, measurement of best-corrected visual acuity (BCVA), complete eye examination, fundus photography, and optical coherence tomography. Fluorescein angiography will be repeated at 6 and 12 months. Each eye in the Ozurdex group can have a maximum total of three Ozurdex insertions at minimum of 4-month intervals in the first year after enrolling into the study.
Drug: Ozurdex

Eyes in the Ozurdex group can have a maximum total of three Ozurdex insertions in the first 12 months after enrolling into the study. The criteria for retreatment with Ozurdex are:

i.The study eye must have shown initial favorable response to prior Ozurdex implant (>10% decrease in central macular thickness with maintenance [change in BCVA of <=1 line] or improvement of visual acuity [increase of BCVA of >1 line]) ii. Interval since last Ozurdex implant should be > 4 and < 12 months. iii. The study eye must show definite evidence of recurrence of macular edema.

Other Names:
  • Dexamethasone intravitreal implant
Active Comparator: Bevacizumab
Patients will be followed at 1 week after the initial bevacizumab injection and then at 1,2, 3,4, 5, and 6 months after implant. Following the 6-month visit, the patients will be examined every 4-8 weeks depending on the status of their macular edema. At each visit patients will be checked for side effects of treatment, measurement of BCVA, complete eye examination, fundus photography, and optical coherence tomography. Fluorescein angiography will be repeated at 6 and 12 months. Eyes in the Bevacizumab group can have a maximum total of twelve (12) bevacizumab injections at minimum of 4-week intervals in the first year after enrolling into the study.
Drug: Bevacizumab
Eyes in the Bevacizumab group can have a maximum total of twelve bevacizumab injections in the first year after enrolling into the study. All patients will receive 6 monthly injections after entering the study. After the sixth injection (at month 5) the interval between injections will be extended to 6 weeks if the study eye has shown initial favorable response to prior intravitreal bevacizumab.
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity
Time Frame: At 12 months
The number of participants that developed 2 or more lines of visual acuity improvement in the study eye. Visual acuity was measured with Snellen eye chart placed 10 feet away from the patient.
At 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Central Subfield Retinal Thickness
Time Frame: At 12 months
Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement
At 12 months
Development of Glaucoma
Time Frame: At 12 months
Intraocular pressure more than 21 mm Hg as measured with applanation tonometry.
At 12 months
Development of Cataract
Time Frame: At 12 months
Development of visually-significant lens opacity based on judgement of examining physician.
At 12 months
Development of Retinal Detachment
Time Frame: At 12 months
Development of rhegmatogenous retinal detachment in the study eye.
At 12 months
Development of Vitreous Hemorrhage
Time Frame: At 12 months
Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy.
At 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arman Mashayekhi

Collaborators

Allergan

Investigators

  • Principal Investigator: Armen Mashayekhi, MD, Wills Eye Hospital IRB Director

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

November 4, 2011

First Submitted That Met QC Criteria

November 10, 2011

First Posted (Estimate)

November 11, 2011

Study Record Updates

Last Update Posted (Actual)

September 3, 2019

Last Update Submitted That Met QC Criteria

August 29, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Wills IRB# 11-089

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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