Topotecan Episcleral Plaque for Retinoblastoma

(STEP-RB Trial)

Overseen By Kaitlyn Flegg

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: The Hospital for Sick Children

Must not be taking: Chemotherapy, Investigational agents

Disqualifiers: Metastatic disease, Allergy to topotecan, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for children with eye cancer that hasn't fully responded to other treatments. It uses a small device placed on the eye to slowly release a cancer-fighting drug directly where it's needed.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot receive chemotherapy or other retinoblastoma treatments within 3 weeks of the study treatment. It's best to discuss your current medications with the study team.

Is Topotecan Episcleral Plaque safe for use in humans?

Research on topotecan, used in different forms for retinoblastoma, shows it is generally safe. Studies in children and rabbits found no significant toxicity when used in the eye, with no harmful effects on vision or overall health. ^{1 2 3 4 5}

How is the Topotecan Episcleral Plaque treatment different from other retinoblastoma treatments?

The Topotecan Episcleral Plaque treatment is unique because it involves delivering the drug topotecan directly to the eye using a plaque, which may allow for targeted treatment of retinoblastoma with potentially fewer side effects compared to systemic chemotherapy. This method is different from traditional treatments that often involve systemic administration or other local delivery methods like intravitreal injections. ^{1 2 3 4 6}

What data supports the effectiveness of the Topotecan Episcleral Plaque treatment for retinoblastoma?

Research shows that topotecan, when used in different forms, has been effective in treating retinoblastoma. For example, a study found that intravitreal topotecan led to the complete disappearance of retinal tumors in children with retinoblastoma, and another study showed that topotecan combined with other drugs helped preserve vision and avoid more invasive treatments. ^{2 4 6 7 8}

Who Is on the Research Team?

Brenda Gallie

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

Children under 18 with active residual or recurrent retinoblastoma in one eye after first-line therapy, or those newly diagnosed with certain types of retinoblastoma without prior treatment. They must have good organ function and performance status, and girls able to have children must use effective birth control. Kids can't join if they have cancer spread outside the eye, allergies to topotecan, other treatments within 3 weeks before the trial starts, uncontrolled illnesses, or are pregnant/breastfeeding.

Inclusion Criteria

My study eye can potentially see and doesn't show signs of cancer spreading outside the eye.

My kidneys are working well.

My blood tests show my bone marrow and platelets are functioning well.

Exclusion Criteria

I am allergic to topotecan, camptothecin, or similar drugs.

I am not pregnant and will stop breastfeeding to start the treatment.

I haven't had chemotherapy or other specific treatments for retinoblastoma within the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Chemoplaque for sustained-release topotecan delivery to treat retinoblastoma

9 weeks

Regular clinic visits and examinations under anaesthesia (EUAs)

Follow-up

Participants are monitored for safety and effectiveness after Chemoplaque removal

4 weeks

Clinic visits for post plaque removal toxicity evaluation

What Are the Treatments Tested in This Trial?

Interventions

• Topotecan Episcleral Plaque

Trial Overview The safety and effectiveness of a new treatment called Topotecan Episcleral Plaque is being tested for kids with a type of eye cancer called retinoblastoma. This study involves gradually increasing doses to find out how much medicine can be given safely while checking how well it works against the cancer.

How Is the Trial Designed?

Group I: Phase I single arm trial Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Published Research Related to This Trial

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]

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 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]

Citations

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

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

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

Ocular Salvage and Vision Preservation Using a Topotecan-Based Regimen for Advanced Intraocular Retinoblastoma. [2022]

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

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

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

Radiotherapy of retinoblastoma. A review of 63 children treated with different irradiation techniques. [2019]

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

¹⁰⁶Ruthenium plaque therapy (RPT) for retinoblastoma. [2012]

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

A phase I study of periocular topotecan in children with intraocular retinoblastoma. [2022]

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]

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

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