Pilot Study of Lucentis Combined With Proton Beam Irradiation in Treating Wet Age-related Macular Degeneration

Study Overview
=================
Brief Summary
-----------------
Because a possible synergism of radiation and inhibitors of vascular endothelial growth factor has been shown in cancer patients and patients with wet macular degeneration, this pilot study is being conducted to determine whether treating wet macular degeneration with a combination of Lucentis and proton beam irradiation is safe. Lucentis is an inhibitor of vascular endothelial growth factor which was recently FDA approved for treatment of wet macular degeneration. It appears to be the most effective therapy thus far for wet macular degeneration among all drugs FDA approved for this condition. If no major safety issues are associated with this combination therapy, a larger study will be conducted to determine whether this combination therapy is more effective than Lucentis monotherapy.

Detailed Description
-----------------
Five subjects diagnosed with wet macular degeneration will be treated with standard of care, i.e. intravitreal Lucentis injection monthly for the first four months and as needed thereafter. Within six weeks of the first Lucentis injection, the eye will also be treated with 24 Gy of proton beam divided into two fractions. Each subject will be followed for 2 yrs with monthly examination.

Official Title
-----------------
Phase 1 Pilot Open Label Prospective Observational Study of Safety and Tolerability of Lucentis Combined With Proton Beam Irradiation in Treating Exudative Age-related Macular Degeneration

Conditions
-----------------
Age-related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: Proton beam irradiation and ranibizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Hgb A1C < 6 Diagnosed with Age-related Macular Degeneration (ARMD) with active subfoveal choroidal neovascular membrane (CNVM), new or recurrent Visual acuity 20/60 to 20/400 Lesion size < 12 Disc Area Submacular hemorrhage less than 75% of total lesion Submacular fibrosis less than 25% of total lesion Candidate for intravitreal Lucentis Exclusion Criteria: 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 CNVM within 1 mm from the disc margin Photodynamic Therapy (PDT) within 3 months 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 Systemic anticoagulation with coumadin Head tremor or h/o claustrophobia precluding positioning for proton irradiation Inability to maintain steady fixation with either eye Diabetes mellitus requiring treatment History of Malignancy treated within 5 years Allergy to Fluorescein dye

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: proton beam with ranibizumab<br>Intervention is 24Gy proton radiation in 2 fractions given within 6 weeks of first dose of intravitreal ranibizumab (0.5mg) drug combined with four monthly doses of intravitreal lucentis and monthly prn lucentis thereafter. | Drug: Proton beam irradiation and ranibizumab<br>* ranibizumab 0.5mg intravitreal monthly x 4, then prn combined with low dose proton beam irradiation 24Gy (2 fractions, 24 hours apart) during the first month of study.<br>* Other names: Lucentis and proton beam;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Ocular Adverse Events | Any ocular adverse event identified by eye examination during the study follow-up will be recorded and determined for possible or probable relation to study treatment. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Change in BCVA From Baseline | change in number of letter read correctly in study eye compared to the number of letters read correctly at baseline, i.e. BCVA (number of letters read correctly) at 24 months minus BCVA (number of letters read correctly) at baseline | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ranibizumab, Age-related macular degeneration, Exudative age-related macular degeneration, Wet macular degeneration, Intravitreal injection, Proton beam irradiation, Lucentis