Intravitreal Aflibercept Injection for Radiation Retinopathy Trial

NCT ID: NCT03085784

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-05

Study Completion Date

2021-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The ARRT trial will assess the safety and efficacy of 2mg aflibercept for the treatment of radiation retinopathy, including maculopathy and optic neuropathy over 52 weeks.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Approximately 40 eyes will be randomized (1:1 ratio) into either Group 1 or Group 2. Slit lamp exam and Indirect ophthalmoscopy will be performed at every study visit, where retinopathy level will be assessed. SD-OCT will be performed at each visit. Fluorescein angiogram will be performed at screen, week 26 and week 52. All other imaging studies will be standard of care at the discretion of the investigator.

This trial will compare the results of 2 groups, with different treatment intervals, to assess the safety of intravitreal Aflibercept injections (IAI) for the treatment of radiation retinopathy. Patients in each group will be followed for a total of 52 weeks.

Group 1: 15 Patients will receive a loading dose of 3 IAI. They will receive 2 mg IAI at screening/baseline, week 4, week 8, and week 12. A follow-up visit will occur at week 12. If the extension criteria are met, the patient will be extended by 2 weeks. The patient will continue to be followed per the treat and extend protocol described below.

Group 2: Patients will not receive a loading dose. They will receive 2 mg IAI at screening/baseline followed by a visit at week 4. At week 4, if the extension criteria are met, the patient will be extended by 2 weeks. The patient will continue to be followed per the treat and extend protocol described below.

Treat \& Extend Protocol Patients can be extended as long as they meet the following criteria -

* Absence of retinal fluid (resolution of intraretinal and subretinal fluid on SD-OCT; Small intraretinal cysts that do not distort foveal contour on SD-OCT are acceptable and can be considered "dry".) AND
* Less than 5 ETDRS letter loss from previous visit due to new or persistent retinal edema.

IAI will be rendered at every visit (treatment at the week 26 mandatory visit will be administered based on the treat and extend status), no earlier than 4 days before the target date and no later than 4 days after the target date. Each extension will be 2 weeks in duration beyond the initial 4-week interval. If the extension criteria are not met on a follow-up visit, the treatment interval will be reduced by 2 weeks. Follow up interval will continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval is reached.

All patients will have a mandatory study visit at Week 52 (final study visit). No study treatment will be administered after week 50 or at a study termination visit. If a patient receives treatment after week 48, they will return 4 weeks after the last clinic visit for the final study visit (instead of at week 52).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Radiation Retinopathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Loading Dose

20 Patients will receive 4, 2 mg IVT Aflibercept (IAI) a month apart, screening/baseline, weeks 4, 8, \& 12. At week 12, patient will be followed \& treated per treat \& extend protocol.

Treat \& Extend Protocol entails patients being extended as long as:

* Absence of retinal fluid (resolution of intraretinal \& subretinal fluid on SD-OCT; Small intraretinal cysts that don't distort foveal contour on SD-OCT are acceptable \& can be considered "dry".) AND
* \< 5 ETDRS letter loss from previous visit, due to new or persistent retinal edema.

Each extension will be 2 weeks in duration beyond the initial 4-week interval. If the extension criteria are not met on a follow-up visit, treatment interval will be reduced by 2 weeks. Follow up interval will continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval is reached.

Group Type EXPERIMENTAL

Aflibercept

Intervention Type DRUG

The investigational product is intravitreal aflibercept injection (IAI), which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. The study duration will be 52 weeks. Vials of drug must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions. The injection volume will be 50μL (0.05 mL) and will be administered to the patients by IVT injection.

Treat and Extend

20 Patients will receive 2 mg IVT Aflibercept (IAI) at screening/baseline followed by a visit at week 4. At week 4, patient will be treated \& followed per the treat \& extend protocol.

Treat \& Extend Protocol entails patients being extended as long as:

* Absence of retinal fluid (resolution of intraretinal \& subretinal fluid on SD-OCT; Small intraretinal cysts that don't distort foveal contour on SD-OCT are acceptable \& can be considered "dry".) AND
* \< 5 ETDRS letter loss from previous visit, due to new or persistent retinal edema.

Each extension will be 2 weeks in duration beyond the initial 4-week interval. If the extension criteria are not met on a follow-up visit, treatment interval will be reduced by 2 weeks. Follow up interval will continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval is reached.

Group Type EXPERIMENTAL

Aflibercept

Intervention Type DRUG

The investigational product is intravitreal aflibercept injection (IAI), which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. The study duration will be 52 weeks. Vials of drug must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions. The injection volume will be 50μL (0.05 mL) and will be administered to the patients by IVT injection.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Aflibercept

The investigational product is intravitreal aflibercept injection (IAI), which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. The study duration will be 52 weeks. Vials of drug must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions. The injection volume will be 50μL (0.05 mL) and will be administered to the patients by IVT injection.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Eylea

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age \> 18 years of age
2. Clinically identifiable radiation retinopathy with evidence of fluid on SD-OCT causing vision loss in the study eye
3. Undergone either ocular or orbital radiation for any primary ocular or orbital cancer within clinical evidence of having radiation retinopathy
4. Willing and able to comply with clinic visits and study-related procedures
5. Provide signed informed consent

Exclusion Criteria

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

1. Metastatic cancer or any active primary cancer, at time of enrollment
2. Prior treatment with anti VEGF in the study within 60 days of screen in the study eye
3. Prior intravitreal or subconjunctival treatment with cortical steroids within 90 days of screen in the study eye
4. Macular ischemia (defined as greater than 5 disc areas), as assessed by the investigator
5. Media opacity obscuring a view of the fundus or any other reason for vision loss other than radiation retinopathy.
6. Evidence of infectious ocular infection, in the study eye, at time of screening
7. Pregnant or breast-feeding women
8. Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly.

* Contraception is not required for men with documented vasectomy. \*\*Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Amy C Schefler, MD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Amy C Schefler, MD

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Amy C Schefler, MD

Role: PRINCIPAL_INVESTIGATOR

Retina Consultants Houston

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Retina Consultants of Houston/Texas Medical Center

Houston, Texas, United States

Site Status

Retina Consultants of Houston

Katy, Texas, United States

Site Status

Retina Consultants of Houston/The Woodlands

The Woodlands, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):974-7. doi: 10.1016/j.ijrobp.2007.11.045.

Reference Type BACKGROUND
PMID: 18313522 (View on PubMed)

Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. doi: 10.1001/archopht.125.6.751.

Reference Type BACKGROUND
PMID: 17562985 (View on PubMed)

Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302.

Reference Type BACKGROUND
PMID: 18698298 (View on PubMed)

Kim IK, Lane AM, Jain P, Awh C, Gragoudas ES. Ranibizumab for the Prevention of Radiation Complications in Patients Treated With Proton Beam Irradiation for Choroidal Melanoma. Trans Am Ophthalmol Soc. 2016 Aug;114:T2.

Reference Type BACKGROUND
PMID: 27630373 (View on PubMed)

Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, Diddie KR, Engstrom RE Jr, Finger PT, Hovland KR, Joffe L, Olsen KR, Wells CG; Collaborative Ocular Melanoma Study Group (COMS Group). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology. 2002 Dec;109(12):2197-206. doi: 10.1016/s0161-6420(02)01277-0.

Reference Type BACKGROUND
PMID: 12466159 (View on PubMed)

Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, Hanson WF, Montague P, Moy CS, Schachat AP, Simpson ER, Straatsma BR, Vine AK, Weingeist TA; Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348-66. doi: 10.1016/s0161-6420(00)00526-1.

Reference Type BACKGROUND
PMID: 11158813 (View on PubMed)

Gunduz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999 May;117(5):609-14. doi: 10.1001/archopht.117.5.609.

Reference Type BACKGROUND
PMID: 10326957 (View on PubMed)

Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28.

Reference Type BACKGROUND
PMID: 23813109 (View on PubMed)

Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. No abstract available.

Reference Type BACKGROUND
PMID: 20142553 (View on PubMed)

Finger PT, Chin KJ. Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27.

Reference Type BACKGROUND
PMID: 21277107 (View on PubMed)

Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011 Jul-Aug;21(4):446-51. doi: 10.5301/EJO.2011.6213.

Reference Type BACKGROUND
PMID: 21218391 (View on PubMed)

Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS. Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma. Retina. 2007 Sep;27(7):903-7. doi: 10.1097/IAE.0b013e31806e6042.

Reference Type BACKGROUND
PMID: 17891015 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ARRT

Identifier Type: -

Identifier Source: org_study_id