Clinical trial NCT01471054: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Wills Eye
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2011-11-11
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity
timeFrame: At 12 months
Secondary outcomes:
measure: Change in Central Subfield Retinal Thickness
timeFrame: At 12 months
measure: Development of Glaucoma
timeFrame: At 12 months
measure: Development of Cataract
timeFrame: At 12 months
measure: Development of Retinal Detachment
timeFrame: At 12 months
measure: Development of Vitreous Hemorrhage
timeFrame: At 12 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Ocular Oncology Service, Wills Eye Institute
state: Pennsylvania
Study officials:
affiliation: Wills Eye Hospital IRB Director
name: Armen Mashayekhi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1001/archopht.120.7.933.
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.
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: 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.
citation: Bakri SJ, Beer PM. Photodynamic therapy for maculopathy due to radiation retinopathy. Eye (Lond). 2005 Jul;19(7):795-9. doi: 10.1038/sj.eye.6701637.
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. doi: 10.1016/S0161-6420(98)98023-X.
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. doi: 10.1016/s0002-9394(02)01938-4.
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. doi: 10.1016/s0161-6420(02)00975-2.
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. doi: 10.1016/s0002-9394(03)00266-6.
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.
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. doi: 10.1001/archopht.125.3.309.
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.
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.