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

NCT06425419 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2023P002259
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Proliferative Vitreo-Retinopathy; Rhegmatogenous Retinal Detachment

Outcome Measures

Primary Outcomes (1)

• Recurrence of rhegmatogenous retinal detachment secondary to PVR

  Investigators will be evaluating whether participant develop a recurrent retinal detachment throughout their follow up after their initial surgery.

  6 months after initial surgery, or last follow-up visit available

Secondary Outcomes (5)

• Best corrected visual acuity (BCVA)

  at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168

• Variation of PVR grade

  at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168

• Retinal reattachment rate at month 6 or last follow up

  at post-operative day 168 (or last follow-up visit available if the participant did not show up at post-operative day 168)

• Recurrence of rhegmatogenous retinal detachment due to any cause

  at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168

• Number of participants and type of intraoperative or postoperative complications

  at time of surgery, and each follow up visit (post-operative day1, 7, 28, 56, 84, 126, 168)

Other Outcomes (1)

• Optical coherence tomography (OCT) of the macula

  at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168

Study Arms (2)

Participants who received intravitreal topotecan

EXPERIMENTAL

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.

Drug: Topotecan

Participants who did not received intravitreal topotecan

NO INTERVENTION

These patients will not be receiving any intervention.

Interventions

Topotecan DRUG

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

Also known as: Hycamtin

Participants who received intravitreal topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts Eye and Ear Infirmary: lead

Related Publications (12)

• 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.

  PMID: 33441730 BACKGROUND

• 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.

  PMID: 33441813 BACKGROUND

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

  PMID: 25196769 BACKGROUND

• 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.

  PMID: 11906814 BACKGROUND

• 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.

  PMID: 22942638 BACKGROUND

• 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.

  PMID: 28844050 BACKGROUND

• 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.

  PMID: 33972235 BACKGROUND

• 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.

  PMID: 32665221 BACKGROUND

• 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.

  PMID: 24789622 BACKGROUND

• 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.

  PMID: 12882951 BACKGROUND

• 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.

  PMID: 24605197 BACKGROUND

• 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.

  PMID: 1867299 BACKGROUND

MeSH Terms

Conditions

Vitreoretinopathy, Proliferative

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Leo Kim, MD, PhD

  Massachusetts Eye and Ear

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leo Kim, MD, PhD

CONTACT

617-391-5896; leo_kim@meei.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Ophthalmology

Model Details: 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.

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: May 22, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share