Intravitreal Topotecan for Proliferative Vitreoretinopathy

(TOPO-PT Trial)

Not yet recruiting at 1 trial location

Overseen By Rajeev H Muni, MD MSc FRCSC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Disqualifiers: Exudative retinal detachment, Diabetic retinopathy, Other ocular surgery, Pregnancy, Bone marrow suppression, 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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called intravitreal topotecan for proliferative vitreoretinopathy (PVR), a serious eye condition that can occur after retinal detachment. The treatment aims to prevent or reduce inflammation and scarring in the eye, potentially improving recovery after retinal detachment surgery. Participants will receive this treatment alongside their surgery, and results will be compared to those of past patients who only underwent standard surgery. Individuals who have had surgery for retinal detachment and are willing to participate might be a good fit for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that injecting intravitreal topotecan into the eye in doses between 5 and 30 micrograms causes no harmful effects. Studies have found no problems with the eye or body from these doses, indicating the treatment's safety for humans. This study uses an 8-microgram dose, well within this safe range. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for proliferative vitreoretinopathy?

Intravitreal topotecan is unique because it introduces a novel way to tackle proliferative vitreoretinopathy by delivering chemotherapy directly into the eye. Most treatments for this condition focus on surgical intervention alone, but topotecan adds a layer of targeted therapy that aims to inhibit cell proliferation, potentially reducing the recurrence of retinal detachment. Researchers are excited because this approach could enhance surgical outcomes and offer a more effective, long-term solution for patients facing this challenging eye condition.

What evidence suggests that intravitreal topotecan might be an effective treatment for proliferative vitreoretinopathy?

This trial will compare the effects of intravitreal topotecan combined with retinal detachment surgery to retinal detachment surgery alone. Research has shown that injecting topotecan directly into the eye may help treat proliferative vitreoretinopathy (PVR), a condition affecting the retina. Early studies found that it reduced inflammation, cell growth, and scarring, which are beneficial for PVR. No side effects appeared with doses between 5 to 30 micrograms per injection, indicating safety at these levels. However, further research is needed to confirm its effectiveness in people. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for patients with rhegmatogenous retinal detachment who are at risk of or currently have proliferative vitreoretinopathy (PVR). Participants should not have any other conditions that could interfere with the study.

Inclusion Criteria

I am willing and able to join the study voluntarily.

I am having or had eye surgery that includes cataract removal and/or retina repair.

I have had surgery for a detached retina.

Exclusion Criteria

I am a woman under 50 and may want to get pregnant during the study.

I have low blood cell counts due to a condition before my current illness.

I have had a type of retinal detachment involving fluid leakage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Preoperative Treatment

Intravitreal topotecan is administered preoperatively within one week before surgery

1 week

1 visit (in-person)

Postoperative Treatment

Intravitreal topotecan is administered one week postoperatively

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intravitreal Topotecan
• Retinal detachment surgery

Trial Overview The study tests intravitreal topotecan, a drug injected into the eye to prevent or treat PVR in patients undergoing retinal detachment surgery. It's a prospective cohort study comparing treated and untreated groups.

How Is the Trial Designed?

Group I: Intravitreal topotecan with retinal detachment surgery Experimental Treatment 2 Interventions

Intravitreal topotecan 8 µg/0.05mL, diluted in sterile saline and administered preoperatively, within one week prior to surgery, as well as one week postoperatively.

Group II: Retinal detachment surgery Active Control 1 Intervention

Historical control patients who previously received standard of care surgery for rhegmatogenous retinal detachment without intravitreal topotecan.

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

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]

Intravitreal topotecan monotherapy demonstrated no retinal toxicity in rabbit models, while melphalan caused significant retinal damage, indicating that topotecan may be a safer alternative for treating retinoblastoma vitreous seeds.

Both topotecan and melphalan were similarly effective in reducing tumor cells in rabbit models, with topotecan achieving a 96% reduction, suggesting that it can be as effective as melphalan without the associated toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study. Bogan, CM., Kaczmarek, JV., Pierce, JM., 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05523869

Study Details | NCT05523869 | Intravitreal Topotecan in ... At doses of 5-30 micrograms per injection, no adverse events have been reported with the use of intravitreal topotecan. Therefore, the current prospective ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10907475/

Proliferative vitreoretinopathy: an update on the current ... In series with established PVR at presentation, the primary overall success rate has been reported between 43 and 69%; although cases can be ...

3. ctv.veeva.com ctv.veeva.com/study/the-safety-and-efficacy-of-intravitreal-topotecan-for-the-treatment-of-proliferative-vitreoretinopat

The Safety and Efficacy of Intravitreal Topotecan for the ... In this study, the efficacy and safety of intravitreal topotecan for the treatment of PVR will be investigated.

4. patlynk.com patlynk.com/trial/NCT06425419

The Safety and Efficacy of Intravitreal Topotecan for ... The study aims to gather data on both the safety and potential benefits of using Topotecan to treat PVR, which could help in developing a more reliable ...

5. trial.medpath.com trial.medpath.com/clinical-trial/e257e8c38257ba24/nct05523869-prospective-cohort-study-intravitreal-topotecan-retinal-detachment

Intravitreal Topotecan in the Repair of Rhegmatogenous ... At doses of 5-30 micrograms per injection, no adverse events have been reported with the use of intravitreal topotecan. Therefore, the current ...

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06425419/

Trial | NCT06425419 The goal of this clinical trial is to evaluate the safety and efficacy of intravitreal topotecan for the treatment of patients with rhegmatogenous retinal ...