Intravitreal Topotecan for Retinal Detachment

(TOPO-RD Trial)

Recruiting at 1 trial location

Overseen By Marko Popovic, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Disqualifiers: Diabetic retinopathy, Bone marrow suppression, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests intravitreal topotecan, a chemotherapy drug administered directly into the eye, for proliferative vitreoretinopathy (PVR), a severe condition that can cause retinal detachment. The researchers aim to determine if this treatment can improve outcomes for individuals with unsuccessful retinal detachment surgeries. Participants must have experienced a previous failed surgery for retinal detachment and have PVR-related issues. Those with certain other eye conditions or health issues, such as diabetic eye disease, are not eligible. If successful, this trial could offer new hope for those facing recurrent retinal detachment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to potential advancements in eye care.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. You can continue any other treatments or medications before and during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that injecting topotecan directly into the eye is safe for humans. At doses between 5 and 30 micrograms per injection, no side effects have been reported, indicating good tolerance at these levels. Even at higher doses, such as 90 micrograms, studies found no harmful effects. This is encouraging for its potential use in treating eye conditions like proliferative vitreoretinopathy (PVR) related to retinal detachment. So far, evidence suggests that topotecan is safe for use in the eye at these tested doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for retinal detachment?

Unlike the standard treatments for retinal detachment, which typically involve procedures like pars plana vitrectomy (PPV) and scleral buckle (SB), the investigational treatment uses intravitreal topotecan. Topotecan is a chemotherapy agent that targets proliferative vitreoretinopathy (PVR), a major cause of retinal detachment recurrence. Researchers are excited about this approach because it introduces a new mechanism of action that directly addresses the underlying issues of PVR, potentially reducing the recurrence of retinal detachment and improving surgical outcomes. This method could offer a promising alternative to existing surgical options by combining surgery with targeted drug therapy.

What evidence suggests that this trial's treatments could be effective for proliferative vitreoretinopathy?

Research has shown that injecting topotecan directly into the eye might help treat proliferative vitreoretinopathy (PVR), a condition that can lead to retinal detachment. In this trial, one group of participants will receive intravitreal topotecan combined with pars plana vitrectomy, with or without scleral buckle. Lab studies have demonstrated topotecan's strong abilities to reduce inflammation and scarring, which are important for managing PVR. This drug has already been used successfully for retinoblastoma, a type of eye cancer, where it helped control tumor growth. Specifically, when used to treat eye tumors in retinoblastoma, topotecan was safe and effective at different doses without causing harmful side effects. These findings suggest that topotecan could also benefit patients with retinal problems like PVR. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific eye condition called rhegmatogenous retinal detachment (RRD) and severe proliferative vitreoretinopathy (PVR), who have had unsuccessful standard surgeries. It's not for those with certain diabetic eye issues, lung disease, other types of retinal detachment, or women under 50 likely to bear children.

Inclusion Criteria

My eye condition is classified as severe retinal detachment.

I have had surgery for a detached retina that didn't work.

I had surgery for repeated retinal detachment due to scar tissue.

Exclusion Criteria

I am scheduled for another eye surgery after my vitrectomy.

I have had a retinal detachment due to pulling or leaking.

I am a woman under 50 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravitreal topotecan with pars plana vitrectomy with or without scleral buckle for RRD with PVR

6-8 weeks

Multiple visits for surgical procedures and follow-up

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular follow-up visits to assess efficacy and safety

What Are the Treatments Tested in This Trial?

Interventions

• Intravitreal Topotecan
• Pars plana vitrectomy
• Scleral Buckle

Trial Overview

The study tests intravitreal topotecan's effectiveness in treating PVR in RRD patients. Participants will receive this drug directly into the eye alongside standard surgical procedures like vitrectomy or scleral buckle to see if it improves outcomes.

How Is the Trial Designed?

Group I: Intravitreal topotecan with pars plana vitrectomy with or without scleral buckle Experimental Treatment 2 Interventions

Patients aged 18 years and older who undergo PPV with or without SB for RRD with PVR grade C or D will be recruited. To be enrolled, patients need to undergo PPV with or without SB for recurrent RRD due to PVR or open globe injury. Surgery can be performed based on the surgeon's discretion. Patients receiving combined phacoemulsification and PPV with or without SB can be included.

Group II: Pars plana vitrectomy with or without scleral buckle Active Control 1 Intervention

Patients assigned to the PPV with or without SB group will undergo three-port PPV with or without SB. Surgery can be performed based on the surgeon's discretion. Patients receiving combined phacoemulsification and PPV with or without SB can be included.

Intravitreal Topotecan is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Hycamtin for:

• Ovarian cancer
• Small cell lung cancer
• Cervical cancer

Approved in United States as Hycamtin for:

• Ovarian cancer
• Small cell lung cancer
• Cervical cancer

Approved in Canada as Hycamtin for:

• Ovarian cancer
• Small cell lung cancer
• Cervical cancer

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

Intravitreal administration of topotecan at a dose of 0.5 μg achieved potentially therapeutic concentrations in the rabbit vitreous, indicating its potential effectiveness for treating intraocular retinoblastoma.

Both 0.5 μg and 5 μg doses of topotecan were found to be safe for the rabbit eye, with no significant retinal toxicity or systemic absorption detected, suggesting a favorable safety profile for clinical translation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma. Buitrago, E., Del Sole, MJ., Torbidoni, A., et al.[2013]

Intravitreal topotecan solutions remain stable for at least 24 hours at room temperature and for 167 days when stored frozen at -20°C, ensuring its availability for treating retinoblastoma in children.

The study confirms that no degradation products appeared in thawed samples, indicating that the formulation is safe and effective for use in clinical settings, particularly in resource-limited institutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the storage of chemotherapeutics for ophthalmic oncology: stability of topotecan solution for intravitreal injection. Bossacoma, F., Cuadrado-Vilanova, M., Vinent, J., et al.[2021]

High-dose intravitreal injections of topotecan (up to 50 μg) in rabbits showed no ocular or systemic toxicity, indicating a potential safe treatment option for retinoblastoma.

The study suggests that repeated high-dose topotecan injections could effectively manage vitreous seeding in retinoblastoma without causing retinal damage, paving the way for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular and systemic toxicity of high-dose intravitreal topotecan in rabbits: Implications for retinoblastoma treatment. Del Sole, MJ., Clausse, M., Nejamkin, P., et al.[2023]

In a study involving 8 children with visually threatening or recurrent intraocular retinoblastoma, periocular topotecan hydrochloride combined with fibrin sealant effectively reduced tumor volume in small tumors, allowing for successful focal therapy in most cases.

The treatment showed minimal toxicity, with no significant ocular or hematological side effects observed, and all treated eyes classified as group A or B were retained after a median follow-up of 11 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periocular topotecan for intraocular retinoblastoma. Mallipatna, AC., Dimaras, H., Chan, HS., et al.[2022]

A study of 50 intravitreal injections of topotecan in 28 eyes of retinoblastoma patients showed that when combined with melphalan, there was a significant decrease in retinal function as measured by ERG amplitude, indicating potential retinal toxicity.

However, when topotecan was administered alone at doses of 20 μg or 30 μg, there was no significant decrease in ERG amplitude, suggesting that these doses of topotecan do not cause retinal toxicity in patients with retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is intravitreal topotecan toxic to retinal function? Nadelmann, J., Francis, JH., Brodie, SE., et al.[2022]

Intravitreal injection of 90 µg of topotecan resulted in complete regression of recurrent retinal tumors in three children with retinoblastoma, demonstrating its efficacy after prior treatments failed.

The treatment was well-tolerated, with no observed toxicity, marking the first human report of this approach for retinal tumors in retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Topotecan 90 µg for Recurrent Solid Retinoblastoma Tumors Is Effective and Not Toxic. Abramson, DH., Francis, JH.[2023]

Topotecan demonstrates antitumor activity against retinoblastoma, both as a standalone treatment and in combination with other agents like carboplatin and vincristine, based on a review of 42 studies including preclinical and clinical data.

The drug shows favorable pharmacokinetics when administered via intravitreal injection or intraophthalmic artery, achieving high concentrations in the vitreous with minimal systemic exposure and low ocular toxicity, although further research is needed to establish optimal dosing and administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular pharmacology of topotecan and its activity in retinoblastoma. Schaiquevich, P., Carcaboso, AM., Buitrago, E., et al.[2022]

Topotecan, when administered via periocular injection or intravenous infusion, can reach the vitreous humor in a rabbit model, indicating its potential effectiveness for treating retinoblastoma.

Despite both administration methods leading to high plasma levels of topotecan, the transfer to the vitreous from the periocular site was minimal, and no local toxicity was observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan vitreous levels after periocular or intravenous delivery in rabbits: an alternative for retinoblastoma chemotherapy. Carcaboso, AM., Bramuglia, GF., Chantada, GL., et al.[2022]

Transcorneal intravitreal injection of topotecan at doses of 1 μg and 2 μg resulted in detectable intraocular concentrations that may be cytotoxic, with significant structural changes observed in the rabbit eyes, including corneal vascularization and retinal atrophy.

Both doses led to low plasma levels of topotecan, but the 2 μg dose showed higher vitreous concentrations and faster absorption, indicating a need for further research to assess the safety of topotecan for treating retinoblastoma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: alternative retinoblastoma treatment. Darsova, D., Pochop, P., Uhlik, J., et al.[2013]

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