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

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called intravitreal topotecan, which is injected directly into the eye. It aims to help patients with severe proliferative vitreoretinopathy (PVR) and rhegmatogenous retinal detachment (RRD). The medication works by reducing inflammation, stopping abnormal cell growth, and preventing scarring inside the eye. Topotecan has been studied for its effectiveness and safety in treating retinoblastoma and has shown promising results in managing vitreous seeds.

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.

What data supports the effectiveness of the drug Intravitreal Topotecan for Retinal Detachment?

Research shows that intravitreal topotecan is effective in treating recurrent solid retinal tumors in retinoblastoma, with complete disappearance of tumors and no observed toxicity in children. This suggests potential effectiveness for other retinal conditions, like retinal detachment, although direct evidence for this specific condition is not available. ^{1 2 3 4 5}

Is intravitreal topotecan safe for use in humans?

Research indicates that intravitreal topotecan, used in treating retinoblastoma, has shown no toxicity in humans at doses up to 90 µg, and animal studies suggest it is safe at even higher doses. No significant side effects, such as retinal damage or systemic toxicity, were observed in these studies. ^{1 4 6 7 8}

How is the drug Intravitreal Topotecan unique for treating retinal detachment?

Intravitreal Topotecan is unique because it is directly injected into the eye, allowing it to target the retina more effectively, which is different from other treatments that may not deliver the drug as precisely to the affected area. This method has been used successfully in treating retinoblastoma, a type of eye cancer, suggesting its potential for other retinal conditions. ^{1 2 4 7 9}

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. Czech Republic pubmed.ncbi.nlm.nih.gov

Topotecan vitreous and plasma levels and retinal toxicity after transcorneal intravitreal delivery in healthy albino rabbits: alternative retinoblastoma treatment. [2013]

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

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

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

Ocular pharmacology of topotecan and its activity in retinoblastoma. [2022]

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

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

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

Periocular topotecan for intraocular retinoblastoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Ocular and systemic toxicity of high-dose intravitreal topotecan in rabbits: Implications for retinoblastoma treatment. [2023]

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

Is intravitreal topotecan toxic to retinal function? [2022]

8. England pubmed.ncbi.nlm.nih.gov

Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma. [2013]

9. England pubmed.ncbi.nlm.nih.gov

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