ProspectiveTrial of Proton Beam Combined With Anti-VEGF Therapy for Exudative Age-related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that proton beam irradiation combined with intravitreal anti-VEGF therapy is safe and potentially more effective than intravitreal anti-VEGF therapy alone in eyes with exudative age-related macular degeneration.

Detailed Description
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Radiation combined with anti-VEGF therapy has been shown to be synergistic in treating cancer and result in sustained tumor regression. On-going clinical trials have shown potential synergism between intravitreal anti-VEGF therapy and epiretinal brachytherapy administered during vitrectomy surgery in treating eyes with exudative age-related macular degeneration (eAMD). In this study, we test the hypothesis that radiation to the macula administered noninvasively via proton beam is well-tolerated in eyes with eAMD when combined with intravitreal anti-VEGF therapy and that this combination therapy may act synergistically to result in sustained treatment effect in eyes with eAMD.

Official Title
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Phase I/II Prospective, Randomized, Double-blinded Study of Intravitreal Anti-VEGF Therapy Combined With Proton Beam Radiation Versus Sham Irradiation in Treating Exudative Age-related Macular Degeneration

Conditions
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Exudative Age-related Macular Degeneration

Intervention / Treatment
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* Drug: 24GyE proton and Anti-VEGF
* Drug: 16GyE and anti-VEGF
* Drug: Sham Irradiation and anti-VEGF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible if the following criteria are met: Ability to provide written informed consent and comply with study assessments for the full duration of the study Age > 50 years Patient related considerations Able to maintain follow-up for at least 24 months. Women must be postmenopausal without a period for at least one year. Diagnosed with Age-related Macular Degeneration (ARMD) with active subfoveal choroidal neovascular membrane (CNVM), newly diagnosed or treated with first dose of anti-VEGF therapy within 6 weeks of enrollment Visual acuity 20/40 to 20/400 Lesion size < 12 Disc Area Submacular hemorrhage less than 75% of total lesion and not involving foveal center Submacular fibrosis less than 25% of total lesion Candidate for intravitreal anti-VEGF therapy Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: Prior enrollment in the study Pregnancy (positive pregnancy test) or lactation Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Participation in another simultaneous medical investigation or trial Previous treatment with Photodynamic Therapy (PDT) or thermal laser in study eye Anti-VEGF therapy within 6 weeks Intravitreal or subtenon's Kenalog within 6 months Intraocular surgery within 3 months or expected in the next 6 months Current or planned participation in other experimental treatments for wet AMD Other concurrent retinopathy or optic neuropathy Other causes of CNVM, i.e. myopic degeneration or ocular histoplasmosis (POHS) Significant media opacity precluding adequate view of the fundus for exam, photography or OCT History of radiation therapy to the head or study eye Diabetes mellitus or hemoglobin A1c > 6 Head tremor or h/o claustrophobia precluding positioning for proton irradiation Inability to maintain steady fixation with either eye History of Malignancy treated within 5 years Allergy to Fluorescein dye

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 24GyE + anti-VEGF<br> | Drug: 24GyE proton and Anti-VEGF<br>* 24GyE proton beam will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy<br>* Other names: 24Gy Proton Beam + Anti-VEGF;|
| Experimental: 16GyE + anti-VEGF<br> | Drug: 16GyE and anti-VEGF<br>* 16GyE of Proton Beam Irradiation will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy<br>* Other names: 16Gy proton beam + Anti-VEGF;|
| Sham Comparator: Sham Irradiation + anti-VEGF<br> | Drug: Sham Irradiation and anti-VEGF<br>* 2 Sessions of Sham Proton Beam Irradiation 24 hrs apart administered 2 to 6 weeks after intravitreal anti-VEGF therapy<br>* Other names: Sham proton beam + anti-VEGF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Eyes With Severe Ocular Adverse | vision loss of 3 or more lines associated with radiation retinopathy or papillopathy | Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Anti-VEGF Injections Administered | efficacy measure | Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exudative Age-related Macular Degeneration, Proton beam irradiation, ranibizumab, bevacizumab, anti-VEGF therapy