Dexamethasone Implant for Retinal Detachment in Uveal Melanoma

NCT ID: NCT04082962

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-11

Study Completion Date

2023-12-07

Brief Summary

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This is an investigator-initiated Phase I study of a single dose of an intravitreally-administered dexamethasone implant (Ozurdex™) in subjects with uveal melanomas (UM) and exudative retinal detachments (ERD: build-up of fluid under the retina that causes it to detach) being treated with proton beam radiation (PBI) or plaque radiotherapy. Although PBI is an effective treatment for UM, ERDs may persist after radiation, leading to vision loss. Effective treatments for ERD are currently lacking. We are conducting this study to evaluate whether Ozurdex™ can help resolve ERDs that occur in patients with UM. Ozurdex™ has been approved by the Food and Drug Administration (FDA) to treat certain ocular conditions such as macular edema, non-infectious uveitis, and diabetic macular edema but it is not approved for use in patients with UM and ERD. This study will determine the safety of the dexamethasone implant and provide preliminary evidence of efficacy in this population.

Detailed Description

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Study Objective: The primary objective of the study will be to determine the safety of the Ozurdex (dexamethasone) intravitreal implant. The secondary objective is to determine if the implant helps to resolve exudative retinal detachment, a secondary complication associated with uveal melanoma.

Background: This is a single site investigator-initiated Phase I study of a single dose of intravitreally administered dexamethasone implant (Ozurdex™) in subjects with choroidal melanomas and exudative retinal detachments being treated with proton beam irradiation or plaque radiation therapy. This is one of the first studies to evaluate the Ozurdex™ implant in this setting. Therefore the primary goal is to evaluate safety.

Patient Population: Twenty patients will be enrolled in this randomized pilot study. Patients must meet the following eligibility criteria to enroll: Tumor thickness ≤ 10 mm, associated serous retinal detachment \> two clock hours in extent, primary treatment of ocular melanoma with proton irradiation or plaque radiotherapy. Males and females \>18 years of age are eligible.

Methods: Patients will be randomized (1:1) to receive the dexamethasone implant or no treatment. A stratified randomization scheme will be performed, with strata defined by tumor height (\< 5mm and 5mm - ≤ 10 mm). Patients will be masked to their treatment assignment.

Patients will be randomly assigned to receive Ozurdex™ (0.7 mg dexamethasone) or no treatment at either (1) the time of their tumor localization (tantalum ring placement) surgery before proton therapy or (2) their surgery removing the plaque following plaque radiotherapy. A sham treatment procedure to maintain the mask will be unnecessary.

Patients will be followed at 6 weeks, 14 weeks, 28 weeks and 54 weeks after administration of the dexamethasone implant. Visual acuity, intraocular pressure, optical coherence tomography, B-scan ultrasonography, wide-angle color photography and full ophthalmological examination will be performed pre-op and on every follow-up visit. Evaluation of adverse events and review of medical history and medication use will be completed at all follow-up visits.

The primary outcome of the study will be to evaluate the safety of the implant. This will be done by monitoring for all adverse effects not related to the melanoma or radiation treatment including significant vision loss, other sight-threatening events, and unforeseen systemic events.

Secondary endpoints include resolution of retinal detachment at 6 and 12 months after implant insertion, visual acuity at 6 and 12 months after implant insertion, and development of iris neovascularization and neovascular glaucoma during the 12 month study period.

Statistical Analysis Plan: There is no formal sample size calculation in a pilot/phase I study. As this is a phase I study, a sample size of 20 patients is chosen, making sure that it is feasible financially and logistically to conduct the study.

Safety Endpoints: Incidence and severity of ocular and systemic adverse events identified by ocular examination, diagnostic tests, and subject reporting will be summarized. Comparisons of these endpoints of study subjects who received treatment may be made with those of control subjects, matched on prognostic factors including tumor size and tumor location. The proportion of treated patients with adverse events will be tabulated by body system, stratified by tumor size and location, and compared to patients in the control arm using Fisher's exact test and other appropriate tests of association.

Efficacy Endpoints: Descriptive statistics will be generated to assess resolution of exudative retinal detachment at 6 months after placement of the Ozurdex implant or no treatment. This is the most important efficacy endpoint. Descriptive statistics will be generated for the following secondary efficacy endpoints: incidence of neovascular glaucoma, incidence of rubeosis, percent of patients with exudative retinal detachment at 12 months, and distribution of visual acuity measures at 6 months and 12 months. All measures will be compared between patients in the treatment arm and those in the control arm of the study.

Conditions

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Exudative Retinal Detachment and Uveal Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Twenty patients will be enrolled in this randomized pilot study. Patients will be randomized (1:1) to receive the dexamethasone implant or no treatment. A stratified randomization scheme will be performed, with strata defined by tumor height (\< 5mm and 5mm - \< 10 mm). Patients with newly diagnosed choroidal melanoma meeting specified eligibility criteria will be randomly assigned to receive Ozurdex™ (0.7 mg dexamethasone) or no treatment at the time of their tumor localization (tantalum ring placement) surgery for patients receiving PBI or at the time of plaque removal for those patients receiving plaque radiotherapy.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Treatment Group

Participants receiving dexamethasone implant.

Group Type EXPERIMENTAL

Dexamethasone intravitreal implant

Intervention Type DRUG

Ozurdex™ is an intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR® solid polymer drug delivery system (NOVADUR™ system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix, which slowly degrades to lactic acid and glycolic acid.). Ozurdex™ is preservative-free. It is supplied in a foil pouch with a single-use plastic applicator.

Non-treatment group (control)

Participants not receiving dexamethasone implant.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Dexamethasone intravitreal implant

Ozurdex™ is an intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR® solid polymer drug delivery system (NOVADUR™ system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix, which slowly degrades to lactic acid and glycolic acid.). Ozurdex™ is preservative-free. It is supplied in a foil pouch with a single-use plastic applicator.

Intervention Type DRUG

Other Intervention Names

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Ozurdex™

Eligibility Criteria

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Inclusion Criteria

* Tumor thickness \<= 10 mm.
* Associated serous retinal detachment extending beyond tumor, \> two clockhours in extent.
* Primary treatment of ocular melanoma with proton irradiation or plaque radiotherapy.

Exclusion Criteria

* Any pre-existing glaucoma.
* History of elevated IOP (\> 25 mm Hg).
* History of steroid response glaucoma.
* Active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva: active ocular herpes simplex, active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
* Any history of ocular herpes simplex.
* Torn or ruptured posterior lens capsule.
* Known hypersensitivity to any components of the dexamethasone intravitreal implant.
* Women of child-bearing potential: pregnant or planning to become pregnant.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ivana K. Kim

OTHER

Sponsor Role lead

Responsible Party

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Ivana K. Kim

Associate Professor of Ophthalmology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ivana K Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School, Massachusetts Eye and Ear

Locations

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Anne Marie Lane

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Char DH, Bove R, Phillips TL. Laser and proton radiation to reduce uveal melanoma-associated exudative retinal detachments. Am J Ophthalmol. 2003 Jul;136(1):180-2.

Reference Type BACKGROUND
PMID: 12834689 (View on PubMed)

Gibran SK, Kapoor KG. Management of exudative retinal detachment in choroidal melanoma. Clin Exp Ophthalmol. 2009 Sep;37(7):654-9. doi: 10.1111/j.1442-9071.2009.02127.x.

Reference Type BACKGROUND
PMID: 19788660 (View on PubMed)

Scotto J, Fraumeni JF Jr, Lee JA. Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. J Natl Cancer Inst. 1976 Mar;56(3):489-91. doi: 10.1093/jnci/56.3.489.

Reference Type BACKGROUND
PMID: 1255781 (View on PubMed)

Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006 Dec;124(12):1684-93. doi: 10.1001/archopht.124.12.1684.

Reference Type BACKGROUND
PMID: 17159027 (View on PubMed)

Gragoudas ES. Proton beam irradiation of uveal melanomas: the first 30 years. The Weisenfeld Lecture. Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4666-73. doi: 10.1167/iovs.06-0659. No abstract available.

Reference Type BACKGROUND
PMID: 17065472 (View on PubMed)

Kivela T, Eskelin S, Makitie T, Summanen P. Exudative retinal detachment from malignant uveal melanoma: predictors and prognostic significance. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2085-93.

Reference Type BACKGROUND
PMID: 11481276 (View on PubMed)

Parrozzani R, Pilotto E, Dario A, Miglionico G, Midena E. Intravitreal triamcinolone versus intravitreal bevacizumab in the treatment of exudative retinal detachment secondary to posterior uveal melanoma. Am J Ophthalmol. 2013 Jan;155(1):127-133.e2. doi: 10.1016/j.ajo.2012.06.026. Epub 2012 Sep 18.

Reference Type BACKGROUND
PMID: 22995029 (View on PubMed)

Kim IK, Lane AM, Jain P, Awh C, Gragoudas ES. Ranibizumab for the Prevention of Radiation Complications in Patients Treated With Proton Beam Irradiation for Choroidal Melanoma. Trans Am Ophthalmol Soc. 2016 Aug;114:T2.

Reference Type BACKGROUND
PMID: 27630373 (View on PubMed)

Malcles A, Nguyen AM, Mathis T, Grange JD, Kodjikian L. Intravitreal dexamethasone implant (Ozurdex(R)) for exudative retinal detachment after proton beam therapy for choroidal melanoma. Eur J Ophthalmol. 2017 Aug 30;27(5):596-600. doi: 10.5301/ejo.5000940. Epub 2017 Feb 8.

Reference Type BACKGROUND
PMID: 28218368 (View on PubMed)

Koehler PJ. Use of corticosteroids in neuro-oncology. Anticancer Drugs. 1995 Feb;6(1):19-33. doi: 10.1097/00001813-199502000-00002.

Reference Type BACKGROUND
PMID: 7756680 (View on PubMed)

Sturdza A, Millar BA, Bana N, Laperriere N, Pond G, Wong RK, Bezjak A. The use and toxicity of steroids in the management of patients with brain metastases. Support Care Cancer. 2008 Sep;16(9):1041-8. doi: 10.1007/s00520-007-0395-8. Epub 2008 Feb 7.

Reference Type BACKGROUND
PMID: 18256860 (View on PubMed)

Other Identifiers

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2019P000127

Identifier Type: -

Identifier Source: org_study_id