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

NCT01471054 | Terminated Phase 2 Results

• 1 other identifier: Wills IRB# 11-089
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in Central Subfield Retinal Thickness

  At 12 months

• Development of Glaucoma

  At 12 months

• Development of Cataract

  At 12 months

• Development of Retinal Detachment

  At 12 months

• Development of Vitreous Hemorrhage

  At 12 months

Study Arms (2)

Ozurdex

EXPERIMENTAL

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

Bevacizumab

ACTIVE COMPARATOR

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

Interventions

Ozurdex DRUG

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.

Also known as: Dexamethasone intravitreal implant

Ozurdex

Bevacizumab DRUG

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.

Also known as: Avastin

Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%).

Sponsors & Collaborators

• Arman Mashayekhi: lead
• Allergan: collaborator

Study Sites (1)

Ocular Oncology Service, Wills Eye Institute

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (14)

• 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.

  PMID: 12096964 BACKGROUND

• 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.

  PMID: 18301032 BACKGROUND

• 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.

  PMID: 19481812 BACKGROUND

• Sutter FK, Gillies MC. Intravitreal triamcinolone for radiation-induced macular edema. Arch Ophthalmol. 2003 Oct;121(10):1491-3. doi: 10.1001/archopht.121.10.1491. No abstract available.

  PMID: 14557194 BACKGROUND

• 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.

  PMID: 18698298 BACKGROUND

• 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.

  PMID: 15359269 BACKGROUND

• 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.

  PMID: 9709753 BACKGROUND

• 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.

  PMID: 12566041 BACKGROUND

• 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.

  PMID: 11986098 BACKGROUND

• 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.

  PMID: 14516818 BACKGROUND

• 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.

  PMID: 19268890 BACKGROUND

• 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.

  PMID: 17353400 BACKGROUND

• 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.

  PMID: 20212197 BACKGROUND

• 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.

  PMID: 21220619 BACKGROUND

MeSH Terms

Conditions

Macular Edema; Uveal Melanoma

Interventions

Calcium Dobesilate; Dexamethasone; Bevacizumab

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Uveal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Could not reach target number of participants

Results Point of Contact

• Title: Arman Mashayekhi, MD
• Organization: Oncology Service, Wills Eye Hospital

arman_mash@yahoo.com

215-928-3105

Study Officials

• Armen Mashayekhi, MD

  Wills Eye Hospital IRB Director

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 11, 2011
• Study Start: April 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 3, 2019
• Results First Posted: January 10, 2019

Record last verified: 2019-08

Locations

US (1)