Prospective Randomized Trial of Proton Beam Combined With Anti-VEGF Therapy for Exudative Age-related Macular Degeneration (AMD) (PBAMD2)

This study is ongoing, but not recruiting participants.
University of California, San Francisco
Information provided by (Responsible Party):
University of California, Davis Identifier:
First received: September 29, 2010
Last updated: December 2, 2015
Last verified: December 2015
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.

Condition Intervention Phase
Exudative Age-related Macular Degeneration
Drug: 24GyE proton and Anti-VEGF
Drug: 16GyE and anti-VEGF
Drug: Sham Irradiation and anti-VEGF
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Number of eyes with 3 or more lines of vision loss from baseline [ Time Frame: Month 12 and 24 ] [ Designated as safety issue: Yes ]
    Incidence of severe vision loss from radiation retinopathy or other causes

Secondary Outcome Measures:
  • number of anti-VEGF therapy [ Time Frame: Month 12 and 24 ] [ Designated as safety issue: No ]
    efficacy measure

  • number of eyes with 3 or more lines of visual acuity gain from baseline [ Time Frame: Month 12 and 24 ] [ Designated as safety issue: No ]
    Efficacy measure

  • Number of eyes with radiation retinopathy or papillopathy [ Time Frame: Month 12 and 24 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: September 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 24GyE + anti-VEGF Drug: 24GyE proton and Anti-VEGF
24GyE proton beam will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy
Other Name: 24Gy Proton Beam + Anti-VEGF
Experimental: 16GyE + anti-VEGF Drug: 16GyE and anti-VEGF
16GyE of Proton Beam Irradiation will be administered in 2 fractions 24 hrs apart 2 to 6 weeks after intravitreal anti-VEGF therapy
Other Name: 16Gy proton beam + Anti-VEGF
Sham Comparator: Sham Irradiation + anti-VEGF Drug: Sham Irradiation and anti-VEGF
2 Sessions of Sham Proton Beam Irradiation 24 hrs apart administered 2 to 6 weeks after intravitreal anti-VEGF therapy
Other Name: Sham proton beam + anti-VEGF

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.

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01213082

United States, California
University of California Davis Eye Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
University of California, San Francisco
Principal Investigator: Susanna S Park, MD PhD University of California, Davis
  More Information

Responsible Party: University of California, Davis Identifier: NCT01213082     History of Changes
Other Study ID Numbers: 201018281-1 
Study First Received: September 29, 2010
Last Updated: December 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
Exudative Age-related Macular Degeneration
Proton beam irradiation
anti-VEGF therapy

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs processed this record on May 23, 2016