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

Macular Edema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01471054
• Other study ID #: Wills IRB# 11-089
• Status: Terminated
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: July 2015

Study information

• Verified date: August 2019
• Source: Wills Eye
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Cystoid Macular Edema
• Edema
• Macular Edema
• Melanoma
• Radiation Maculopathy
• Radiation Retinopathy
• Retinal Diseases
• Uveal Melanoma
• Uveal Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Ocular Oncology Service, Wills Eye Institute	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Arman Mashayekhi	Allergan

Country where clinical trial is conducted

United States, 

References & Publications (14)

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

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. — View Citation

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. — View Citation

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. — View 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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

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