Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Macular Edema Cystoid Macular Edema Uveal Melanoma Radiation Maculopathy Radiation Retinopathy	Drug: Ozurdex Drug: Bevacizumab	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration

MedlinePlus related topics: Edema Melanoma Retinal Disorders

Drug Information available for: Dexamethasone Dexamethasone sodium phosphate Dexamethasone acetate Bevacizumab

Genetic and Rare Diseases Information Center resources: APUDoma Carcinoid Tumor Intraocular Melanoma Neuroepithelioma Uveal Diseases

U.S. FDA Resources

Further study details as provided by Wills Eye:

Primary Outcome Measures:

Proportion of eyes showing >=2 lines of improvement in best-corrected visual acuity [ Time Frame: At 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in central subfield retinal thickness [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
Development of glaucoma [ Time Frame: At 12 months ] [ Designated as safety issue: Yes ]
Development of cataract [ Time Frame: At 12 months ] [ Designated as safety issue: Yes ]
Development of retinal detachment [ Time Frame: At 12 months ] [ Designated as safety issue: Yes ]
Development of vitreous hemorrhage [ Time Frame: At 12 months ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	20
Study Start Date:	December 2014
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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 (>10% increase in central macular thickness with worsening of visual acuity [decrease of BCVA of >1 line not attributable to other causes]). iv. None of the exclusion criteria for Ozurdex implant must be present. Other Name: 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 (>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]). If after extension, the macular edema recurs (>10% increase in central macular thickness with worsening of visual acuity [decrease of BCVA of >1 line not attributable to other causes based on the judgment of the investigators]), then the interval between injections will be reduced to 4 weeks without further attempts to extend the injection interval. Other Name: Avastin

Arms

Assigned Interventions

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 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 (>10% increase in central macular thickness with worsening of visual acuity [decrease of BCVA of >1 line not attributable to other causes]).

iv. None of the exclusion criteria for Ozurdex implant must be present.

Other Name: 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 (>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]). If after extension, the macular edema recurs (>10% increase in central macular thickness with worsening of visual acuity [decrease of BCVA of >1 line not attributable to other causes based on the judgment of the investigators]), then the interval between injections will be reduced to 4 weeks without further attempts to extend the injection interval.

Other Name: Avastin

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 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 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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01471054

Contacts


Contact: Arman Mashayekhi, MD	215-928-3105

Locations


United States, Pennsylvania
Ocular Oncology Service, Wills Eye Institute	Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Arman Mashayekhi, MD
Principal Investigator: Arman Mashayekhi, MD
Sub-Investigator: Carol L Shields, MD
Sub-Investigator: Jerry A Shields, MD
Sub-Investigator: Sara E Lally, MD

Sponsors and Collaborators

Arman Mashayekhi

Allergan

More Information

Publications:

Shields CL, Cater J, Shields JA, Chao A, Krema H, Materin M, Brady LW. Combined plaque radiotherapy and transpupillary thermotherapy for choroidal melanoma: tumor control and treatment complications in 270 consecutive patients. Arch Ophthalmol. 2002 Jul;120(7):933-40.

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.

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.

Sutter FK, Gillies MC. Intravitreal triamcinolone for radiation-induced macular edema. Arch Ophthalmol. 2003 Oct;121(10):1491-3.

Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302.

Bakri SJ, Beer PM. Photodynamic therapy for maculopathy due to radiation retinopathy. Eye (Lond). 2005 Jul;19(7):795-9.

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.

Benhamou N, Massin P, Haouchine B, Audren F, Tadayoni R, Gaudric A. Intravitreal triamcinolone for refractory pseudophakic macular edema. Am J Ophthalmol. 2003 Feb;135(2):246-9.

Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002 May;109(5):920-7.

Scott IU, Flynn HW Jr, Rosenfeld PJ. Intravitreal triamcinolone acetonide for idiopathic cystoid macular edema. Am J Ophthalmol. 2003 Oct;136(4):737-9.

Williams GA, Haller JA, Kuppermann BD, Blumenkranz MS, Weinberg DV, Chou C, Whitcup SM; Dexamethasone DDS Phase II Study Group. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol. 2009 Jun;147(6):1048-54, 1054.e1-2. doi: 10.1016/j.ajo.2008.12.033. Epub 2009 Mar 9.

Kuppermann BD, Blumenkranz MS, Haller JA, Williams GA, Weinberg DV, Chou C, Whitcup SM; Dexamethasone DDS Phase II Study Group. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol. 2007 Mar;125(3):309-17.

Haller JA, Kuppermann BD, Blumenkranz MS, Williams GA, Weinberg DV, Chou C, Whitcup SM; Dexamethasone DDS Phase II Study Group. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol. 2010 Mar;128(3):289-96. doi: 10.1001/archophthalmol.2010.21.

Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, Li XY, Cui H, Whitcup SM; Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011 May;129(5):545-53. doi: 10.1001/archophthalmol.2010.339. Epub 2011 Jan 10.


Responsible Party:	Arman Mashayekhi, Principal Investigator, Assistant Professor, Wills Eye
ClinicalTrials.gov Identifier:	NCT01471054 History of Changes
Other Study ID Numbers:	Wills IRB# 11-089
Study First Received:	November 4, 2011
Last Updated:	November 2, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Wills Eye:


Plaque radiotherapy Brachytherapy Macular edema Cystoid macular edema Uveal melanoma	Radiation maculopathy Radiation retinopathy Ozurdex Dexamethasone intravitreal implant

Additional relevant MeSH terms:


Edema Macular Edema Melanoma Retinal Diseases Uveal Neoplasms Eye Diseases Eye Neoplasms Macular Degeneration Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors	Nevi and Melanomas Retinal Degeneration Signs and Symptoms Uveal Diseases BB 1101 Bevacizumab Dexamethasone Dexamethasone 21-phosphate Dexamethasone acetate Angiogenesis Inhibitors Angiogenesis Modulating Agents Anti-Inflammatory Agents Antiemetics Antineoplastic Agents Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on February 25, 2015