Intravitreal Topotecan for Proliferative Vitreoretinopathy

(TOPO-PT Trial)

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

394 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Intravitreal Topotecan for treating Proliferative Vitreoretinopathy?

Intravitreal Topotecan has shown effectiveness in treating retinoblastoma, a type of eye cancer, by reaching significant levels in the eye and minimizing side effects in the rest of the body. This suggests it could be effective for other eye conditions like Proliferative Vitreoretinopathy. ^{1 2 3 4 5}

Is intravitreal topotecan safe for use in humans?

Intravitreal topotecan has been used safely in humans for treating retinoblastoma, a type of eye cancer, without causing harm to the retina (the light-sensitive layer at the back of the eye). Studies have shown no toxicity in patients receiving this treatment. ^{1 2 3 6 7}

How is the drug intravitreal topotecan different from other treatments for proliferative vitreoretinopathy?

Intravitreal topotecan is unique because it is administered directly into the eye, which allows it to target the affected area more precisely. This method has been used effectively in treating retinoblastoma, a type of eye cancer, suggesting it may offer a novel approach for conditions like proliferative vitreoretinopathy where direct eye treatment is beneficial. ^{1 2 3 4 7}

What is the purpose of this trial?

Intravitreal topotecan exhibits strong anti-inflammatory, anti-proliferative, and anti-fibrotic properties, making it a promising option for preventing and treating proliferative vitreoretinopathy in rhegmatogenous retinal detachment. Preclinical studies have demonstrated its efficacy in proliferative vitreoretinopathy models, where no adverse events have been reported for doses of 5 µg to 30 µg. This prospective, matched cohort study aims to assess the therapeutic efficacy and safety of intravitreal topotecan for preventing and treating proliferative vitreoretinopathy in rhegmatogenous retinal detachment patients.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Optimizing the storage of chemotherapeutics for ophthalmic oncology: stability of topotecan solution for intravitreal injection. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Is intravitreal topotecan toxic to retinal function? [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Topotecan vitreous levels after periocular or intravenous delivery in rabbits: an alternative for retinoblastoma chemotherapy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic analysis of topotecan after intra-vitreal injection. Implications for retinoblastoma treatment. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Intravitreal Topotecan 90 µg for Recurrent Solid Retinoblastoma Tumors Is Effective and Not Toxic. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study. [2022]