Intravitreal Aflibercept Injection for Radiation Retinopathy Trial

Radiation Retinopathy Clinical Trial

— ARRT  

Official title:

Intravitreal Aflibercept Injection (IAI) for Radiation Retinopathy Trial (ARRT)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03085784
• Other study ID #: ARRT
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 5, 2017
• Est. completion date: October 2021

Study information

• Verified date: December 2020
• Source: Greater Houston Retina Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Radiation Retinopathy
• Retinal Diseases

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Retina Consultants of Houston/Texas Medical Center	Houston	Texas
United States	Retina Consultants of Houston	Katy	Texas
United States	Retina Consultants of Houston/The Woodlands	The Woodlands	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Amy C Schefler, MD	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (12)

Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. — View Citation

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. — View Citation

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. — View Citation

Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. — View Citation

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. — View Citation

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. — View Citation

Gündüz 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. — View Citation

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. — View Citation

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. Erratum in: Ophthalmology. 2004 Aug;111(8):1514. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of intravitreal Aflibercept for the treatment of radiation retinopathy - Assessed by incidence of adverse events.	The primary objective of the study is to assess the safety of 2 mg intravitreal Aflibercept injections (IAI) for the treatment of radiation retinopathy including maculopathy and optic neuropathy. Assessed by incidence of adverse events.	52 Weeks
Secondary	Resolution of macular edema (CRT)	Resolution of macular edema as measured by mean change in central retinal thickness	52 Weeks
Secondary	Resolution of macular edema (% dry)	Resolution of macular edema as measured by % of patients who achieve a dry macula	52 Weeks
Secondary	Stabilization and improvement in visual acuity	Stabilization and improvement in visual acuity as measured by the mean change in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity	52 Weeks
Secondary	Dosing frequency of intravitreal aflibercept injections	Dosing frequency of IAI as measured by number of injections	52 Weeks
Secondary	Incidence of neovascularization, vitreous hemorrhage, and need for vitrectomy	Percentage of patients avoiding the development of increased neovascularization, vitreous hemorrhage, and need for vitrectomy	52 Weeks
Secondary	Resolution of retinal hemorrhage, retinal exudates, optic disc edema, and capillary non-perfusion	Percentage of patients with resolution of retinal hemorrhages, retinal exudates, optic disc edema, capillary non-perfusion	52 Weeks