Role of Intravitreal Aflibercept Injection for the Treatment of Radiation Maculopathy

• Sponsor: Larkin Community Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02586727
• Collaborator: (none)
• Enrollment: 40
• Arms: 2
• Duration (Months): 58

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the safety of intravitreal aflibercept injection in treating visually compromising radiation maculopathy secondary to treatment of uveal melanoma by iodione-125 brachytherapy. The study will consist of two arms of 25 patients each (totaling 50 patients). Subjects in arm 1 will undergo treatment every 6 weeks. Subjects in arm 2 will undergo treatment and if improvement is documented at the following evaluation the next treatment will be extended by two weeks. Secondary objectives of the study include evaluation and analysis of visual acuity, number of injections, macular edema, and vascular activity between both arms.

Condition or Disease	Intervention/Treatment	Phase
Adverse Effect of Radiation Therapy	Drug: aflibercept	Phase 2

Detailed Description

This study will consist of 2 simultaneous treatment arms: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Treatment will be given at each visit. Patients with improved radiation maculopathy (SD-OCT analysis) will extend re-evaluation by two weeks (e.g. first interval 6 weeks; second interval 10 weeks; third interval 12 weeks, etc). Patients with increased radiation maculopathy (SD-OCT analysis) will have re-evaluation decreased by one week. Both arms will consist of 25 subjects (eyes). Fluorescein angiography will be completed at baseline, after the 4th injection (or within three weeks of week 24 for the TAE arm), and at the end of the study in all patients. Spectral domain OCT, and clinical evaluation including visual acuity will be assessed every visit in all patients. Radiation maculopathy will be graded every visit in all patients in a blinded fashion using the following classification system: Grade 1 indicates extrafoveal, noncystoid edema; grade 2, extrafoveal cystoid edema; grade 3, foveal noncystoid edema; grade 4, mild-to-moderate foveal cystoid edema; grade 5, severe foveal cystoid edema and grade 6 subretinal fluid. All patients will undergo comprehensive evaluation including adverse event questioning at each study timepoint. Patients in the six-week dosing arm will receive a total of 9 intravitreal aflibercept injections during the study window while the TAE treatment group will receive a maximum of 9 with a minimum of 5.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Role of Intravitreal Aflibercept Injection for the Treatment of Radiation Maculopathy
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: six week dosing regimen arm Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit.	Drug: aflibercept; This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.; Other Names: Eylea
Active Comparator: treat and extend dosing regimen arm Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval.	Drug: aflibercept; This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.; Other Names: Eylea

Outcome Measures

Primary Outcome Measures

1. Mean Best Corrected Visual Acuity (BCVA) in Patients Treated With Intravitreal Aflibercept Injections for the Management of Radiation Maculopathy. [12 months]

   BCVA will be measured with letter optotypes. A lower value indicates a better outcome.

Secondary Outcome Measures

1. Role of Intravitreal Aflibercept Injection on Central Retinal Thickness for the Treatment of Radiation Maculopathy. [12 months]

   Central retinal thickness will be evaluated with OCT. A lower value considered a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A Patient must meet the following criteria to be eligible for inclusion in the study:

1. 21 years of age and over

2. 20/800 or better visual acuity

3. Must have received previous treatment for radiation maculopathy within the last 4-26 weeks

4. Any presence of macular edema (evaluated by SD-OCT) caused by radiation retinopathy

5. Willing and able to comply with clinic visits and study-related procedures

6. Provide signed informed consent

Exclusion Criteria:

• A patient who meets any of the following criteria will be excluded from the study:

1. Patients less than 21 years of age.

2. Patients with mental disability or any other condition that precludes the acquisition of an sdOCT image such as (nystagmus, neck disease, etc.)

3. Patients who have previously been treated with intravitreal triamcinolone acetonide for macular edema (signs of recalcitrant disease)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Larkin Community Hospital

Investigators

• Principal Investigator: Timothy G Murray, MD, MBA, Murray Ocular Oncology & Retina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 15, 2015

More Information

Publications

None provided.

• Responsible Party: Larkin Community Hospital
• ClinicalTrials.gov Identifier: NCT02586727
• Other Study ID Numbers: LCH-1-012015
• First Posted: Oct 26, 2015
• Last Update Posted: May 11, 2021
• Last Verified: Aug 1, 2019

• Keywords provided by Larkin Community Hospital: Radiation Retinopathy; aflibercept
• Additional relevant MeSH terms: Macular Degeneration; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Six Week Dosing Regimen Arm	Treat and Extend Dosing Regimen Arm
Arm/Group Description	Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.	Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.
Period Title: Overall Study
STARTED	20	20
COMPLETED	19	20
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Six Week Dosing Regimen Arm	Treat and Extend Dosing Regimen Arm	Total
Arm/Group Description	Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.	Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 60%	7 35%	19 47.5%
>=65 years	8 40%	13 65%	21 52.5%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	62	67.3	64.7
Sex: Female, Male (Count of Participants)
Female	12 60%	8 40%	20 50%
Male	8 40%	12 60%	20 50%
Race/Ethnicity, Customized (Count of Participants)
White, Non-Hispanic	19 95%	18 90%	37 92.5%
Hispanic	1 5%	2 10%	3 7.5%
Region of Enrollment (Count of Participants)
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Mean Best Corrected Visual Acuity (BCVA) in Patients Treated With Intravitreal Aflibercept Injections for the Management of Radiation Maculopathy.
Description	BCVA will be measured with letter optotypes. A lower value indicates a better outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Baseline study entry mean BCVA was 20/63 (Logmar 0.498)

Arm/Group Title	Six Week Dosing Regimen Arm	Treat and Extend Dosing Regimen Arm
Arm/Group Description	Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.	Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.
Measure Participants	20	20
Mean (Full Range) [Log MAR (Visual Acuity)]	0.425	0.548

2. Secondary Outcome

Title	Role of Intravitreal Aflibercept Injection on Central Retinal Thickness for the Treatment of Radiation Maculopathy.
Description	Central retinal thickness will be evaluated with OCT. A lower value considered a better outcome.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Six Week Dosing Regimen Arm	Treat and Extend Dosing Regimen Arm
Arm/Group Description	Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.	Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.
Measure Participants	20	20
Measure eye	20	20
Mean (Full Range) [microns]	298	294

Adverse Events

Time Frame	2 years
Arm/Group Title	Six Week Dosing Regimen Arm		Treat and Extend Dosing Regimen Arm
Arm/Group Description	Patients will receive an intravitreal aflibercept injection the first visit, and then again every six weeks. Treatment will be given at each visit. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.		Patients will receive an intravitreal aflibercept injection the first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward. Patients with decreased radiation maculopathy by one grade or more will extend re-evaluation by two weeks. Patients with increased radiation maculopathy by one grade or more will have re-evaluation decreased by one week. Patients that show no maculopathy grade change will remain at the same re-evaluation interval. aflibercept: This study will consist of 2 simultaneous treatment arms of aflibercept: A six week dosing regimen arm and a treat and extend (TAE) dosing regimen arm, total duration 54 weeks. In the TAE arm the patients will receive an intravitreal aflibercept injection first visit, again at the second visit at 6 weeks, and then begin treat and extend from second injection forward.
All Cause Mortality
	Six Week Dosing Regimen Arm		Treat and Extend Dosing Regimen Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Six Week Dosing Regimen Arm		Treat and Extend Dosing Regimen Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Six Week Dosing Regimen Arm		Treat and Extend Dosing Regimen Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.