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

This study has been completed.
Sponsor:
Collaborators:
University of California, San Francisco
Genentech, Inc.
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00517010
First received: August 15, 2007
Last updated: June 28, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Age-related Macular Degeneration
Drug: Proton beam irradiation and ranibizumab
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence and Severity of Ocular Adverse Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 1. Change in BCVA From Baseline [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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


Enrollment: 6
Study Start Date: May 2007
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: proton beam with ranibizumab
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
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.
Other Name: Lucentis and proton beam

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

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517010

Sponsors and Collaborators
University of California, Davis
University of California, San Francisco
Genentech, Inc.
Investigators
Principal Investigator: Susanna S Park, MD PhD University of California, Davis
  More Information

Publications:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Published data

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT00517010     History of Changes
Other Study ID Numbers: 200715285  100,481 
Study First Received: August 15, 2007
Results First Received: December 2, 2015
Last Updated: June 28, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Findings have been presented at national and international venues and published in scientific peer-reviewed journal

Keywords provided by University of California, Davis:
Age-related macular degeneration
Exudative age-related macular degeneration
Wet macular degeneration
Intravitreal injection
Proton beam irradiation
Lucentis
Ranibizumab

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 21, 2016