Adverse Effect of Radiation Therapy
Conditions
Keywords
Radiation Retinopathy, aflibercept
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.
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.
Interventions
DRUGaflibercept
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.
Sponsors
Larkin Community Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 20 |
| 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.
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. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Six Week Dosing Regimen Arm | Treat and Extend Dosing Regimen Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 13 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 7 Participants | 19 Participants |
| Age, Continuous | 62 Years | 67.3 Years | 64.7 Years |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White, Non-Hispanic | 19 Participants | 18 Participants | 37 Participants |
| Region of Enrollment United States | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Mean Best Corrected Visual Acuity (BCVA) in Patients Treated With Intravitreal Aflibercept Injections for the Management of Radiation Maculopathy.
BCVA will be measured with letter optotypes. A lower value indicates a better outcome.
Time frame: 12 months
Population: Baseline study entry mean BCVA was 20/63 (Logmar 0.498)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Six Week Dosing Regimen Arm | Mean Best Corrected Visual Acuity (BCVA) in Patients Treated With Intravitreal Aflibercept Injections for the Management of Radiation Maculopathy. | 0.425 Log MAR (Visual Acuity) |
| Treat and Extend Dosing Regimen Arm | Mean Best Corrected Visual Acuity (BCVA) in Patients Treated With Intravitreal Aflibercept Injections for the Management of Radiation Maculopathy. | 0.548 Log MAR (Visual Acuity) |
Secondary
Role of Intravitreal Aflibercept Injection on Central Retinal Thickness for the Treatment of Radiation Maculopathy.
Central retinal thickness will be evaluated with OCT. A lower value considered a better outcome.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Six Week Dosing Regimen Arm | Role of Intravitreal Aflibercept Injection on Central Retinal Thickness for the Treatment of Radiation Maculopathy. | 298 microns |
| Treat and Extend Dosing Regimen Arm | Role of Intravitreal Aflibercept Injection on Central Retinal Thickness for the Treatment of Radiation Maculopathy. | 294 microns |