Clinical trial NCT01213082: ProspectiveTrial of Proton Beam Combined With Anti-VEGF Therapy for Exudative Age-related Macular Degeneration (AMD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Exudative Age-related Macular Degeneration
Keywords: Exudative Age-related Macular Degeneration
Proton beam irradiation
ranibizumab
bevacizumab
anti-VEGF therapy
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2010-10-01
Enrollment: 34
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent of Eyes With Severe Ocular Adverse
timeFrame: Month 24
Secondary outcomes:
measure: Number of Anti-VEGF Injections Administered
timeFrame: Month 24
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Eye Center
state: California
Study officials:
affiliation: University of California, Davis
name: Susanna S Park, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Evans JR, Igwe C, Jackson TL, Chong V. Radiotherapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 Aug 26;8(8):CD004004. doi: 10.1002/14651858.CD004004.pub4.