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Nevus

Nevi and Melanomas

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Ranibizumab

Angiogenesis Inhibitors

Growth Inhibitors

Intravitreal Ranibizumab 0.5mg at the time of radioactive plaque insertion

Carol L Shields, MD

Uveal Melanoma is the most common primary intraocular malignancy in adulthood. Eye preserving treatments can deliver equivalent life prognosis in the management of small and medium sized uveal melanomas, as compared to enucleation. Plaque radiotherapy has emerged as the most common eye-preserving treatment in the current management of uveal melanoma, but is complicated by visual loss in approximately 70% of patients at 10 years follow-up. Strategies for the prevention and early treatment of radiation retinopathy/maculopathy need to be developed to improve visual outcomes following plaque treatment. Ranibizumab (Lucentis) is the antigen binding fragment of a recombinant, humanized monoclonal antibody, which inhibits the activity of vascular endothelial growth factor A, a mediator in the development of choroidal neovascularization. Lucentis is commonly used in the eye for eye conditions such as age related macular degeneration. This study will investigate the possible benefit of Anti-VEGF therapy (Lucentis) in reducing the incidence of radiation complications following plaque radiation for uveal melanoma.

Intravitreal Ranibizumab for the Prevention of Radiation Maculopathy Following Plaque Radiotherapy

A Randomized Control Trial of Intravitreal Ranibizumab (Lucentis) for the Prevention of Radiation Maculopathy Following Plaque Radiotherapy for Choroidal Melanoma

Shields, Shields and Associates

Symptoms and General Pathology

Macular Edema

Edema

Uveal Neoplasms

Eye Neoplasms

Uveal Diseases

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Bevacizumab

Dexamethasone

Dexamethasone acetate

BB 1101

Antineoplastic Agents, Immunological

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

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.

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.

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.

Ozurdex

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.

Armen Mashayekhi, MD

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.

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.

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

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.

Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement

Intraocular pressure more than 21 mm Hg as measured with applanation tonometry.

Development of visually-significant lens opacity based on judgement of examining physician.

Development of rhegmatogenous retinal detachment in the study eye.

Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy.

Allergan

Arman Mashayekhi

Principal Investigator, Assistant Professor

Patients will be followed at 1 week after Ozurdex insertion (0.7 mg) and then at 1,2, 3,4, 5, and 6 months. Afterwards, patients will be seen every 2 months. At each visit patients will undergo 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 of 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.

Patients will be followed at 1 week after the initial bevacizumab injection and then at 1,2, 3,4, 5, and 6 months. Afterwards, the patients will be examined every 4-8 weeks. 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.

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.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Could not reach target number of participants

Arman Mashayekhi, MD

Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity

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 outcome of treatment, including change in central macular thickness.

Patients will be followed at 1 week after intravitreal bevacizumab injection 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 outcome of treatment, including change in central macular thickness.

We were not able to measure central macular thickness at 12 months in one patient in the Ozurdex group due to advanced cataract.

Change in Central Subfield Retinal Thickness

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, including increased intraocular pressure.

Patients will be followed at 1 week after intravitreal bevacizumab injection 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, including increased intraocular pressure.

Development of Glaucoma

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, including cataract.

Patients will be followed at 1 week after intravitreal bevacizumab injection 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, including cataract.

Development of Cataract

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, including retinal detachment.

Patients will be followed at 1 week after intravitreal bevacizumab injection 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, including retinal detachment.

Development of Retinal Detachment

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, including vitreous hemorrhage.

Patients will be followed at 1 week after intravitreal bevacizumab injection 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, including vitreous hemorrhage.

Development of Vitreous Hemorrhage

Patients will be followed at 1 week after Ozurdex insertion (0.7 mg) and then at 1,2, 3,4, 5, and 6 months. Afterwards, patients will be seen every 2 months. At each visit patients will undergo 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 of 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.

Overall Study

Patients will receive intravitreal ranibizumab on a monthly basis depending on response to treatment

intravitreal ranibizumab monthly for 4 months, and then every month thereafter until month 12.

ranibizumab

Paul T Finger, MD

This is a Phase I clinical trial to test the safety and tolerability of intravitreal ranibizumab in the treatment of radiation retinopathy following plaque brachytherapy for patients with choroidal melanoma using the incidence and severity of events criteria.

The secondary objective is to assess the efficacy of intravitreal ranibizumab on regression of radiation retinopathy by ophthalmic examination, fundus photography, fluorescein angiography, and optical coherence tomography, as well as visual acuity.

Following plaque brachytherapy as treatment for choroidal melanoma, patients may develop radiation retinopathy. Radiation retinopathy is a progressive condition that leads to blindness in over 50% of cases within 5 years of treatment.

Vascular endothelial growth factor (VEGF) protein is believed to play a critical role in angiogenesis and radiation retinopathy. It is one of the key contributors to physiological or pathological conditions that can stimulate both the formation of new blood vessels and normal vessel incompetence. Ranibizumab is a recently approved vascular endothelial growth factor (VEGF) inhibitor shown to be effective in treating exudative macular degeneration. Ranibizumab binds to and inhibits vascular endothelial growth factor A (VEGF-A), which has been shown to cause neovascularization and leakage in models of ocular angiogenesis.

This is an open label, non-randomized active treatment, Phase I trial to assess the safety and tolerability of intravitreal ranibizumab and its ability to reduce radiation retinopathy and potentially limit vision loss associated with this disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intravitreal Ranibizumab for the Prevention of Radiation Maculopathy Following Plaque Radiotherapy	NCT00540930	Uveal Melanoma Radiation Retin... Radiation Macul...	Ranibizumab	18 Years -	Shields, Shields and Associates
Dexamethasone Intravitreal Implant for Treatment of Macular Edema After Plaque Radiotherapy of Uveal Melanoma	NCT01471054	Macular Edema Cystoid Macular... Uveal Melanoma Radiation Macul... Radiation Retin...	Ozurdex Bevacizumab	18 Years -	Wills Eye
Effect of Intravitreal Ranibizumab on Radiation Retinopathy Following Plaque Brachytherapy for Choroidal Melanoma	NCT00750399	Radiation Retin... Choroidal Melan...	Ranibizumab ranibizumab	21 Years -	The New York Eye Cancer Center
Effect of Intravitreal Ranibizumab on Radiation Retinopathy Following Plaque Brachytherapy for Choroidal Melanoma	NCT00750399	Radiation Retin... Choroidal Melan...	Ranibizumab ranibizumab	21 Years -	The New York Eye Cancer Center

Spots Global Cancer Trial Database for radiation retinopathy