Back to resultsDexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma
Primary Purpose
Macular Edema, Cystoid Macular Edema, Uveal Melanoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ozurdex
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Macular Edema focused on measuring Plaque radiotherapy, Brachytherapy, Macular edema, Cystoid macular edema, Uveal melanoma, Radiation maculopathy, Radiation retinopathy, Ozurdex, Dexamethasone intravitreal implant
Eligibility Criteria
Inclusion criteria:
- Patient age 18 years or more.
- Uveal melanoma treated with I-125 plaque radiotherapy.
- Visual acuity between 20/40 to 20/400 secondary to post-radiation macular edema.
- Central subfield retinal thickness > 300 micron.
- Duration of macular edema < 12 months.
- No potential contributing causes of decreased vision other than macular edema.
Exclusion criteria:
- Visual acuity worse than 20/400 or better than 20/40.
- Monocular patient or poor vision in the non-study eye (<20/80).
- History of vitrectomy surgery.
- Panretinal photocoagulation or intraocular surgery within 3 months of enrollment.
- Concomitant or previous radiation optic neuropathy.
- Use of periocular, intravitreal, or systemic steroids within 6 month of enrollment in the study eye.
- Use of intravitreal VEGF antagonist within 6 weeks of enrollment.
- History of ocular hypertension or glaucoma, or intraocular pressure (IOP)>21 mmHg.
- History of steroid-induced glaucoma in either eye.
- Active ocular infection or history of herpetic eye infection.
- Clinically significant epiretinal membrane in the study eye.
- Iris neovascularization in the study eye.
- Clinically significant media opacity preventing acquisition of good-quality optical coherence tomography (OCT) in the study eye.
- Aphakia or anterior chamber intraocular lens.
- Poorly controlled diabetes (Hemoglobin A1c level >13%).
- Poorly controlled hypertension (Systolic pressure > 160 mm Hg or diastolic pressure > 90 mm Hg).
- Pregnancy (women of childbearing age should have negative pregnancy test and use contraception).
- 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.
- Interval between plaque radiotherapy for uveal melanoma and intended date of dexamethasone intravitreal implant of less than 6 months.
- Evidence of activity or inadequate regression of the treated uveal melanoma after plaque radiotherapy (based on the judgment of the study investigators).
- Known allergy or hypersensitivity to any of the study medications or their components.
- History of prior myocardial infarction or stroke.
Sites / Locations
- Ocular Oncology Service, Wills Eye Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ozurdex
Bevacizumab
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity
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.
Secondary Outcome Measures
Change in Central Subfield Retinal Thickness
Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement
Development of Glaucoma
Intraocular pressure more than 21 mm Hg as measured with applanation tonometry.
Development of Cataract
Development of visually-significant lens opacity based on judgement of examining physician.
Development of Retinal Detachment
Development of rhegmatogenous retinal detachment in the study eye.
Development of Vitreous Hemorrhage
Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy.
Full Information
NCT ID
NCT01471054
First Posted
November 4, 2011
Last Updated
August 29, 2019
Sponsor
Arman Mashayekhi
Collaborators
Allergan
1. Study Identification
Unique Protocol Identification Number
NCT01471054
Brief Title
Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma
Official Title
Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Could not enroll enough patients.
Study Start Date
April 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Arman Mashayekhi
Collaborators
Allergan
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Edema, Cystoid Macular Edema, Uveal Melanoma, Radiation Maculopathy, Radiation Retinopathy
Keywords
Plaque radiotherapy, Brachytherapy, Macular edema, Cystoid macular edema, Uveal melanoma, Radiation maculopathy, Radiation retinopathy, Ozurdex, Dexamethasone intravitreal implant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ozurdex
Arm Type
Experimental
Arm Description
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.
Arm Title
Bevacizumab
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ozurdex
Other Intervention Name(s)
Dexamethasone intravitreal implant
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity
Description
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.
Time Frame
At 12 months
Secondary Outcome Measure Information:
Title
Change in Central Subfield Retinal Thickness
Description
Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement
Time Frame
At 12 months
Title
Development of Glaucoma
Description
Intraocular pressure more than 21 mm Hg as measured with applanation tonometry.
Time Frame
At 12 months
Title
Development of Cataract
Description
Development of visually-significant lens opacity based on judgement of examining physician.
Time Frame
At 12 months
Title
Development of Retinal Detachment
Description
Development of rhegmatogenous retinal detachment in the study eye.
Time Frame
At 12 months
Title
Development of Vitreous Hemorrhage
Description
Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy.
Time Frame
At 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patient age 18 years or more.
Uveal melanoma treated with I-125 plaque radiotherapy.
Visual acuity between 20/40 to 20/400 secondary to post-radiation macular edema.
Central subfield retinal thickness > 300 micron.
Duration of macular edema < 12 months.
No potential contributing causes of decreased vision other than macular edema.
Exclusion criteria:
Visual acuity worse than 20/400 or better than 20/40.
Monocular patient or poor vision in the non-study eye (<20/80).
History of vitrectomy surgery.
Panretinal photocoagulation or intraocular surgery within 3 months of enrollment.
Concomitant or previous radiation optic neuropathy.
Use of periocular, intravitreal, or systemic steroids within 6 month of enrollment in the study eye.
Use of intravitreal VEGF antagonist within 6 weeks of enrollment.
History of ocular hypertension or glaucoma, or intraocular pressure (IOP)>21 mmHg.
History of steroid-induced glaucoma in either eye.
Active ocular infection or history of herpetic eye infection.
Clinically significant epiretinal membrane in the study eye.
Iris neovascularization in the study eye.
Clinically significant media opacity preventing acquisition of good-quality optical coherence tomography (OCT) in the study eye.
Aphakia or anterior chamber intraocular lens.
Poorly controlled diabetes (Hemoglobin A1c level >13%).
Poorly controlled hypertension (Systolic pressure > 160 mm Hg or diastolic pressure > 90 mm Hg).
Pregnancy (women of childbearing age should have negative pregnancy test and use contraception).
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.
Interval between plaque radiotherapy for uveal melanoma and intended date of dexamethasone intravitreal implant of less than 6 months.
Evidence of activity or inadequate regression of the treated uveal melanoma after plaque radiotherapy (based on the judgment of the study investigators).
Known allergy or hypersensitivity to any of the study medications or their components.
History of prior myocardial infarction or stroke.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armen Mashayekhi, MD
Organizational Affiliation
Wills Eye Hospital IRB Director
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ocular Oncology Service, Wills Eye Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
12096964
Citation
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Results Reference
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18301032
Citation
Horgan N, Shields CL, Mashayekhi A, Teixeira LF, Materin MA, Shields JA. Early macular morphological changes following plaque radiotherapy for uveal melanoma. Retina. 2008 Feb;28(2):263-73. doi: 10.1097/IAE.0b013e31814b1b75.
Results Reference
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19481812
Citation
Horgan N, Shields CL, Mashayekhi A, Salazar PF, Materin MA, O'Regan M, Shields JA. Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial. Ophthalmology. 2009 Jul;116(7):1383-90. doi: 10.1016/j.ophtha.2009.01.051. Epub 2009 May 30.
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Citation
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Citation
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Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology. 1998 Aug;105(8):1425-9. doi: 10.1016/S0161-6420(98)98023-X.
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Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma
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