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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment for retinoblastoma, a type of eye cancer, using a topotecan episcleral plaque to deliver chemotherapy directly to the eye. The trial focuses on children under 18 with active retinoblastoma in one eye after completing their first treatment. This treatment may suit those who still have vision potential in the affected eye and show no signs of cancer spreading outside the eye. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this novel therapy.

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 there any evidence suggesting that Topotecan Episcleral Plaque is likely to be safe for humans?

Research has shown that topotecan, applied directly to the eye using a small device called an episcleral plaque, is being tested for safety in treating retinoblastoma, a type of eye cancer. Studies have found that this method allows controlled drug release, potentially reducing side effects. Previous patients generally tolerated this approach well, with manageable side effects.

As this trial is in an early stage, it primarily aims to understand possible side effects and the body's response to the treatment. While detailed results are not yet available, the focus of this phase is on safety, with close monitoring of any serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for retinoblastoma, which often include chemotherapy or radiation, the Topotecan Episcleral Plaque offers a new delivery method by applying the drug directly onto the eye. This allows for a higher concentration of the drug to reach the tumor while minimizing systemic exposure and potential side effects. Researchers are excited because this localized approach could provide a more effective and safer option for treating retinoblastoma, potentially improving outcomes for young patients.

What evidence suggests that this treatment might be an effective treatment for retinoblastoma?

Research has shown that topotecan, when administered directly to the eye, effectively treats retinoblastoma, a type of eye cancer. Studies indicate that topotecan can kill cancer cells and shrink tumors. This trial tests the topotecan episcleral plaque as a new method to deliver the drug directly to the eye, potentially enhancing its effectiveness and reducing side effects. Early findings suggest this approach could be promising for patients who have not responded to other treatments. ^{2 5 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04428879

Study Details | NCT04428879 | Topotecan Episcleral ... This study will evaluate the safety and efficacy of topotecan delivered directly to the eye using a novel sustained-release topotecan episcleral plaque (also ...

2. trialx.com trialx.com/clinical-trials/listings/251390/topotecan-episcleral-plaque-for-treatment-of-retinoblastoma/

Topotecan Episcleral Plaque for Treatment of ... This study will evaluate the safety and efficacy of topotecan delivered directly to the eye using a novel sustained-release topotecan episcleral ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0008418224001790

Digital retinoblastoma documentation supports care and ... Each child's eCCRB timeline shows treatments and dates. The SwimmerRB tool presents eCCRB data for research with time “0” start of intervention.

4. withpower.com withpower.com/trial/phase-1-retinoblastoma-5-2020-88fc6

Topotecan Episcleral Plaque for Retinoblastoma (STEP- ... Research shows that topotecan, when used in different forms, has been effective in treating retinoblastoma. For example, a study found that intravitreal ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2742478

DEPICT HEALTH Supports Clinical Trial of Sustained-release ... Purpose : Outcomes for 8,000 children newly diagnosed with retinoblastoma each year depend where they live (globally 70% die, with resources and knowledge > ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04156347

Study Details | NCT04156347 | Topotecan Episcleral ... This study will evaluate the safety and efficacy of topotecan delivered directly to the eye using a novel sustained-release topotecan episcleral delivery system ...

7. clinicaltrial.be clinicaltrial.be/fr/details/457958?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Retinoblastoma Phase II Expanded Access Clinical Trial -... To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma by measuring the rate and severity of ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04428879/topotecan-episcleral-plaque-for-treatment-of-retinoblastoma

Topotecan Episcleral Plaque for Treatment of ... This study will evaluate the safety and efficacy of topotecan delivered directly to the eye using a novel sustained-release topotecan episcleral plaque.