Intravitreal Topotecan in the Repair of Rhegmatogenous Retinal Detachment With Proliferative Vitreoretinopathy (TOPO-RD)

A Prospective Matched Cohort Study of Intravitreal Topotecan in the Repair of Rhegmatogenous Retinal Detachment With Proliferative Vitreoretinopathy

Intravitreal topotecan has anti-inflammatory, anti-proliferative and anti-fibrotic activity that we hypothesize may exhibit high efficacy for the treatment of proliferative vitreoretinopathy (PVR) in patients with rhegmatogenous retinal detachment (RRD). A high efficacy for intravitreal topotecan has been exhibited in cell cultures of PVR. At the same time, intravitreal topotecan has been routinely used in the treatment of vitreous seeds from retinoblastoma. At doses of 5-30 micrograms per injection, no adverse events have been reported with the use of intravitreal topotecan. Therefore, the current prospective matched phase II trial aims to investigate the efficacy and safety of intravitreal topotecan for severe PVR in patients with RRD.

Study Overview

• Status: Recruiting
• Conditions: Proliferative Vitreoretinopathy in Rhegmatogenous Retinal Detachment
• Intervention / Treatment: Procedure: Pars plana vitrectomy with or without scleral buckle; Drug: Intravitreal topotecan

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rajeev Muni, MD; Phone Number: 416-867-7411; Email: rajeev.muni@utoronto.ca
• Study Contact Backup: Name: Marko Popovic, MD; Phone Number: 416-867-7411; Email: marko.popovic@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's Hospital
      • Contact: Rajeev Muni; Phone Number: (416) 867-7411
    • Toronto, Ontario, Canada, M4Y 1H1
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Peter Kertes, MD; Phone Number: 416-480-4244

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

To be enrolled, patients need to meet the following inclusion criteria:

1. patients aged 18 years and older
2. patients who undergo PPV and/or SB for recurrent RRD due to PVR
3. patients with RRD and PVR grade C or D
4. patients who have failed standard of care surgery for RRD in the same eye previously. In order to satisfy this inclusion criterion, patients need to have previously received at least one vitreoretinal surgery for RRD, including pneumatic retinopexy, pars plana vitrectomy and/or scleral buckle, and to have clinical documentation supporting re-detachment of the retina after one or more vitreoretinal surgeries for RRD in the same eye. This cohort of patients is expected to have an extremely guarded visual prognosis and visual potential.
5. patients who are voluntarily able and willing to participate Patients undergoing combined phacoemulsification and PPV and/or SB will also be included. Any surgical technique will be considered, including relaxing retinotomy or retinectomy during PPV.

The following subject exclusion criteria will be considered:

1. patients with a history of tractional or exudative retinal detachment
2. patients with severe non-proliferative or proliferative diabetic retinopathy
3. patients with other planned ocular surgery following PPV
4. patients with primary RRD
5. female patients of childbearing age (i.e. less than 50 years old).
6. patients with pre-existing bone marrow suppression or cytopenias
7. patients with pre-existing interstitial lung disease (ILD) Any other medications or treatments, including rescue therapy, will be permitted before and/or during the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravitreal topotecan with pars plana vitrectomy with or without scleral buckle	Procedure: Pars plana vitrectomy with or without scleral buckle; Standard three-port pars plana vitrectomy with or without scleral buckle.; Drug: Intravitreal topotecan; Patients meeting all inclusion criteria and not meeting exclusion criteria will be assigned to receive pars plana vitrectomy with or without scleral buckle with intravitreal topotecan 8 µg/0.1mL, administered preoperatively within one week from surgery, intraoperatively during surgery, as well as postoperatively at 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks, for a total of 7 injections.
Active Comparator: Pars plana vitrectomy with or without scleral buckle	Procedure: Pars plana vitrectomy with or without scleral buckle; Standard three-port pars plana vitrectomy with or without scleral buckle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrent RRD secondary to PVR	6 months or last follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Best corrected visual acuity	6 months or last follow-up
Proliferative vitreoretinopathy grade	6 months or last follow-up
Retinal reattachment rate	6 months or last follow-up
Complications	6 months or last follow-up
Best corrected visual acuity change from baseline	6 months or last follow-up

Collaborators and Investigators

• Sponsor: Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Diseases; Retinal Detachment; Dissociative Disorders; Vitreoretinopathy, Proliferative; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: TOPO-RD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No