The Safety and Efficacy of Intravitreal Topotecan for the Treatment of Proliferative Vitreoretinopathy

NCT ID: NCT06425419

Last Updated: 2025-12-02

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

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-04-01

Study Completion Date

2027-03-01

Brief Summary

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The goal of this clinical trial is to evaluate the safety and efficacy of intravitreal topotecan for the treatment of patients with rhegmatogenous retinal detachment due to proliferative vitreoretinopathy (PVR) or resulting from an open globe injury, and compare the outcomes to those who do no receive intravitreal topotecan. The main objectives it aims to achieve are:

* to study the safety profile of intravitreal topotecan in the treatment of PVR
* to evaluate the efficacy of intravitreal topotecan in treating PVR.

Post-consent, participants will:

* undergo vitrectomy (with or without scleral buckle) as part of standard treatment for retinal detachment.
* receive intravitreal topotecan at the time of surgery, post-operative day 7 and post-operative day 28 (if randomized to receive the medication)
* come in at post-operative day 1, 7, 28, 56, 84, 126 and 168 to undergo a complete ophthalmic exam along with a fundus photography and optical coherence tomography of the macula, have their intraocular pressure and visual acuity measured and their adverse events monitored, if any.

Researchers will compare participants who receive intravitreal topotecan for PVR to those who do not to see if there is a significant variability in recurrence of retinal detachment, rate of retinal reattachment and PVR grade 6 months after surgery.

Detailed Description

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Rhegmatogenous retinal detachment (RRD) is an acute, sight-threatening condition that occurs after separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) due to the presence of a retinal break. Proliferative vitreoretinopathy (PVR) represents growth of ectopic fibrocellular growth on the surface of, within and underneath the retina. PVR is hypothesized to occur secondary to the migration of RPE cells to the peri-retina, leading to a mesenchymal transition into contractile myofibroblasts. PVR affects 5-10% of RRDs and is the most common cause of surgical failure in RRD.

Given that PVR involves a pro-inflammatory and pro-fibrotic cellular response, adjuvants such as corticosteroids and antimetabolites such as 5-fluorouracil have been attempted in the treatment of this condition. Overall, the efficacy results of these treatments have been mixed, and no standard of care adjuvant therapy has emerged.

Topotecan is a chemotherapeutic agent that acts as a topoisomerase inhibitor. It is most commonly administered intravitreally for patients with refractory or recurrent vitreous seeds from retinoblastoma, and shows high efficacy in this setting. At the same time, intravitreal topotecan administered at doses of 5-30µg has been associated with no ocular or systemic complications or adverse electroretinogram changes. To the best of available knowledge, topotecan has not been administered for the treatment of proliferative vitreoretinopathy. Topotecan has anti-inflammatory, anti-proliferative and anti-fibrotic activity that is hypothesized to exhibit high efficacy for the treatment of PVR. In this study, the efficacy and safety of intravitreal topotecan for the treatment of PVR will be investigated.

Conditions

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Proliferative Vitreoretinopathy Proliferative Vitreo-Retinopathy Rhegmatogenous Retinal Detachment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Half of the patients will receive intravitreal topotecan at the time of surgery. Randomization will be done based on a computer-generated list that would randomly allocate each of the 50 participants to being either in the treatment arm or in the control arm, in a particular order. Results will be printed on a card put in sealed envelopes that would be given to each research subject based on the allocation order given by that computer-generated list.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Participants who received intravitreal topotecan

These are the patients who will be receiving intravitreally 20 micrograms of topotecan in a 1cc syringe during surgery, at the post-operative day 7 and at the post-operative day 28.

Group Type EXPERIMENTAL

Topotecan

Intervention Type DRUG

20 micrograms of intravitreal topotecan given in a 1 cc tuberculin syringe at a concentration of 20 mcg/20mcL.

Participants who did not received intravitreal topotecan

These patients will not be receiving any intervention.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Topotecan

20 micrograms of intravitreal topotecan given in a 1 cc tuberculin syringe at a concentration of 20 mcg/20mcL.

Intervention Type DRUG

Other Intervention Names

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Hycamtin

Eligibility Criteria

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Inclusion Criteria

* Patients \> 18 years old
* Patients presenting with retinal detachment due with PVR (grade C or higher) or retinal detachment associated with open globe trauma
* Patients undergoing vitrectomy or vitrectomy with scleral buckle as part of standard care.

Exclusion Criteria

* Patient unable to give consent
* Patient unable to follow-up
* Females of childbearing age who are pregnant at the time of recruitment. A pregnancy test will be done to all women of ages 18-55 prior to surgery to ensure they are not pregnant at the time of recruitment.
* Patients with a history of tractional or exudative retinal detachment.
* Patients with other planned ocular surgery following PPV
* Active or chronic or recurrent uncontrolled ocular or systemic disease
* Active or history of chronic or recurrent inflammatory eye disease
* Diagnosis of severe nonproliferative or proliferative diabetic retinopathy or vasoproliferative disease in the operative eye
* Signs of ocular infection at presentation in either eye
* Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
* No Light Perception vision in the operative eye
* Failure to achieve intraoperative reattachment
* Patient with silicone oil instilled in the operative eye at time of presentation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Massachusetts Eye and Ear Infirmary

OTHER

Sponsor Role lead

Responsible Party

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Leo Am Kim, M.D.

Associate Professor of Ophthalmology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Leo Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear

Central Contacts

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Leo Kim, MD, PhD

Role: CONTACT

617-391-5896

References

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Cepeda MS, Boston R, Farrar JT, Strom BL. Comparison of logistic regression versus propensity score when the number of events is low and there are multiple confounders. Am J Epidemiol. 2003 Aug 1;158(3):280-7. doi: 10.1093/aje/kwg115.

Reference Type BACKGROUND
PMID: 12882951 (View on PubMed)

Kim J, Shin W. How to do random allocation (randomization). Clin Orthop Surg. 2014 Mar;6(1):103-9. doi: 10.4055/cios.2014.6.1.103. Epub 2014 Feb 14.

Reference Type BACKGROUND
PMID: 24605197 (View on PubMed)

Machemer R, Aaberg TM, Freeman HM, Irvine AR, Lean JS, Michels RM. An updated classification of retinal detachment with proliferative vitreoretinopathy. Am J Ophthalmol. 1991 Aug 15;112(2):159-65. doi: 10.1016/s0002-9394(14)76695-4.

Reference Type BACKGROUND
PMID: 1867299 (View on PubMed)

Ohman T, Gawriyski L, Miettinen S, Varjosalo M, Loukovaara S. Molecular pathogenesis of rhegmatogenous retinal detachment. Sci Rep. 2021 Jan 13;11(1):966. doi: 10.1038/s41598-020-80005-w.

Reference Type BACKGROUND
PMID: 33441730 (View on PubMed)

Mysore Y, Del Amo EM, Loukovaara S, Hagstrom M, Urtti A, Kauppinen A. Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous. Sci Rep. 2021 Jan 13;11(1):980. doi: 10.1038/s41598-020-80127-1.

Reference Type BACKGROUND
PMID: 33441813 (View on PubMed)

Claes C, Lafeta AP. Proliferative vitreoretinopathy. Dev Ophthalmol. 2014;54:188-95. doi: 10.1159/000360466. Epub 2014 Aug 26.

Reference Type BACKGROUND
PMID: 25196769 (View on PubMed)

Pastor JC, de la Rua ER, Martin F. Proliferative vitreoretinopathy: risk factors and pathobiology. Prog Retin Eye Res. 2002 Jan;21(1):127-44. doi: 10.1016/s1350-9462(01)00023-4.

Reference Type BACKGROUND
PMID: 11906814 (View on PubMed)

Sadaka A, Giuliari GP. Proliferative vitreoretinopathy: current and emerging treatments. Clin Ophthalmol. 2012;6:1325-33. doi: 10.2147/OPTH.S27896. Epub 2012 Aug 14.

Reference Type BACKGROUND
PMID: 22942638 (View on PubMed)

Rao R, Honavar SG, Sharma V, Reddy VAP. Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma. Br J Ophthalmol. 2018 Apr;102(4):490-495. doi: 10.1136/bjophthalmol-2017-310641. Epub 2017 Aug 26.

Reference Type BACKGROUND
PMID: 28844050 (View on PubMed)

Bogan CM, Kaczmarek JV, Pierce JM, Chen SC, Boyd KL, Calcutt MW, Bridges TM, Lindsley CW, Nadelmann JB, Liao A, Hsieh T, Abramson DH, Francis JH, Friedman DL, Richmond A, Daniels AB. Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study. Br J Ophthalmol. 2022 Feb;106(2):288-296. doi: 10.1136/bjophthalmol-2020-318529. Epub 2021 May 10.

Reference Type BACKGROUND
PMID: 33972235 (View on PubMed)

Nadelmann J, Francis JH, Brodie SE, Muca E, Abramson DH. Is intravitreal topotecan toxic to retinal function? Br J Ophthalmol. 2021 Jul;105(7):1016-1018. doi: 10.1136/bjophthalmol-2020-316588. Epub 2020 Jul 14.

Reference Type BACKGROUND
PMID: 32665221 (View on PubMed)

Ghassemi F, Shields CL, Ghadimi H, Khodabandeh A, Roohipoor R. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma. JAMA Ophthalmol. 2014 Aug;132(8):936-41. doi: 10.1001/jamaophthalmol.2014.414.

Reference Type BACKGROUND
PMID: 24789622 (View on PubMed)

Other Identifiers

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2023P002259

Identifier Type: -

Identifier Source: org_study_id

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