Clinical trial NCT00517010: Pilot Study of Lucentis Combined With Proton Beam Irradiation in Treating Wet Age-related Macular Degeneration
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Age-related Macular Degeneration
Keywords: Age-related macular degeneration
Exudative age-related macular degeneration
Wet macular degeneration
Intravitreal injection
Proton beam irradiation
Lucentis
Ranibizumab
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: Genentech, Inc.
First posted: 2007-08-16
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence and Severity of Ocular Adverse Events
timeFrame: 24 months
Secondary outcomes:
measure: 1. Change in BCVA From Baseline
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
affiliation: University of California, Davis
name: Susanna S Park, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park SS, Daftari I, Phillips T, Morse LS. Three-year follow-up of a pilot study of ranibizumab combined with proton beam irradiation as treatment for exudative age-related macular degeneration. Retina. 2012 May;32(5):956-66. doi: 10.1097/IAE.0b013e31822a8d6a.