Chemoplaque for Retinoblastoma

Overseen By Brian Marr, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Targeted Therapy Technologies, LLC

Must not be taking: Chemotherapy, Investigational agents

Disqualifiers: Optic nerve invasion, Metastatic retinoblastoma, 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: 5

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for advanced or recurring retinoblastoma, a type of eye cancer in children, using chemoplaque, a localized chemotherapy treatment. The aim is to determine if chemoplaque can safely and effectively save the affected eye, avoiding the need for removal. Children under 8 years old with advanced retinoblastoma in one eye or who have not responded to other treatments might be suitable candidates. Participants should have some vision in the affected eye and no signs of cancer spreading outside the eye. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to advance care for retinoblastoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received chemotherapy or other retinoblastoma treatments within 3 weeks before starting the study treatment.

What prior data suggests that this chemoplaque is safe for treating retinoblastoma?

Research shows that topotecan, the main ingredient in the chemoplaque treatment, has been studied for safety and effectiveness. In earlier studies, researchers applied topotecan directly to the eye using a special device called an episcleral plaque. This method showed promise in treating retinoblastoma, a type of eye cancer in children. Safety was a major focus, and results suggest that this delivery system is generally well-tolerated.

Topotecan has also been used safely in other treatments for children for over 20 years, supporting its safety record. While some mild side effects may occur, serious side effects are not commonly reported.

Overall, research provides a positive view of the safety of using chemoplaque for treating retinoblastoma. However, joining a clinical trial is a personal choice, and discussing any concerns with a healthcare team is important. ^{1 2 3 4 5}

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

Chemoplaque is unique because it delivers a sustained release of topotecan directly to the eye through a method called episcleral application. Unlike traditional treatments for retinoblastoma, which often involve systemic chemotherapy or radiation, Chemoplaque targets the tumor locally, potentially reducing side effects and improving drug concentration at the site of the tumor. This targeted delivery method is exciting because it offers the possibility of more effective treatment with fewer risks, which is a significant advance in managing this serious eye cancer in children.

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

Studies have shown that Chemoplaque, which delivers the drug Topotecan directly to the eye, effectively treats retinoblastoma. Topotecan stops cancer cells from multiplying, helping to shrink tumors. Early results suggest it targets the tumor more precisely, potentially saving the eye when other treatments have failed. In previous patients, this method showed promising results in controlling tumor growth and preserving vision. While more research continues, these early signs indicate that Chemoplaque could be a good option for advanced retinoblastoma cases.

Are You a Good Fit for This Trial?

This trial is for children under 8 years old with advanced or recurrent retinoblastoma, potentially facing eye removal. They must have some vision potential in the affected eye and no signs of cancer spread outside the eye. Kids need to be generally healthy with good blood counts and kidney function.

Inclusion Criteria

My white blood cell count is high enough for treatment.

My kidney function, measured by creatinine clearance or GFR, is sufficient.

I am under 8 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Chemoplaque is applied to the eye for sustained delivery of chemotherapy over 8 weeks

8 weeks

4 visits (in-person) on Day 0, Day 28, Day 56, and Day 84

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) on Day 84

What Are the Treatments Tested in This Trial?

Interventions

• Chemoplaque

Trial Overview The study tests a treatment called Chemoplaque (Episcleral Topotecan) for saving eyes from being removed due to retinoblastoma. It aims to find out how safe it is, how well it works, and what's the best dose for treating this type of eye cancer.

How Is the Trial Designed?

Group I: Chemoplaque Experimental Treatment 1 Intervention

Chemoplaque (also referred to as Episcleral Topotecan) treatment will involve single application of the Episcleral Topotecan 1.2 mg dose that delivers sustained delivery for 8 weeks.

Who Is Running the Clinical Trial?

Targeted Therapy Technologies, LLC

Lead Sponsor

Trials

5

Recruited

80+

Columbia-New York-Presbyterian Morgan Stanley Children's Hospital

Collaborator

Trials

1

Recruited

30+

Morgan Stanley Children's Hospital

Collaborator

Trials

10

Recruited

5,012,000+

Published Research Related to This Trial

A new chemoreduction protocol using intravenous cyclophosphamide and a reduced dose of carboplatin was successful in treating retinoblastoma, achieving a 75% success rate in preserving eyes among 56 treated eyes over a mean follow-up of 101 months.

The study indicates that this treatment approach is safe and effective, allowing for reduced carboplatin use while effectively controlling tumor progression without the need for enucleation or external beam radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoreduction improves eye retention in patients with retinoblastoma: a report from the German Retinoblastoma Reference Centre. Künkele, A., Jurklies, C., Wieland, R., et al.[2015]

In a study involving six albino rabbits, repeated intravitreal injections of 0.008 mg of carboplatin showed significant reductions in electroretinogram (ERG) amplitudes, indicating potential retinal toxicity, but no histopathological changes were observed.

The findings suggest that 0.008 mg may be the highest safe dose for carboplatin in treating retinoblastoma, although caution is advised in directly applying these results to human patients due to differences between rabbit and human retinal responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes. Pochop, P., Darsova, D., Uhlik, J., et al.[2015]

Intravitreal melphalan (IVM) is an effective treatment for vitreous seeding in retinoblastoma, with a 59% eye-saving rate and a 100% survival rate at 1 year for treated eyes, based on a study of 27 patients over a median follow-up of 65 months.

Patients with bilateral retinoblastoma who received IVM had significantly better outcomes compared to those receiving standard treatments, highlighting the potential of IVM as a preferred option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Survival Following Intravitreal Melphalan as Adjuvant Treatment for Vitreous Retinoblastoma Seeding. Alahmadi, G., Maktabi, AMY., Sesma, G., et al.[2023]

Intravitreal carboplatin showed initial effectiveness in treating vitreous seeds in retinoblastoma, with complete regression observed in all four patients after a varying number of injections, but safety concerns arose due to significant retinal toxicity in one patient leading to vision loss and cataract formation.

The study was ultimately terminated after higher doses failed to achieve complete regression in subsequent patients, and all three of these patients responded well to an alternative treatment, intravitreal melphalan, suggesting that while carboplatin may have potential, safer options are available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial. King, BA., Wilson, MW., Kaluzny, T., et al.[2023]

Subconjunctival carboplatin was found to be effective in treating intraocular retinoblastoma, with significant tumor responses observed in 3 out of 5 eyes with vitreous disease.

The treatment was generally safe, with only minor toxicities such as transient periorbital edema and one case of optic atrophy, indicating the need for further studies to assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of subconjunctival carboplatin for intraocular retinoblastoma. Abramson, DH., Frank, CM., Dunkel, IJ.[2022]

Intraocular delivery of carboplatin effectively inhibits tumor growth in a dose-dependent manner in transgenic mice with hereditary retinoblastoma, with a significant reduction in tumor burden observed at doses as low as 1.4 micrograms.

However, retinal toxicity was noted in rabbits at doses of 10 micrograms or higher, indicating a need for careful dose management to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local carboplatin therapy in transgenic murine retinoblastoma. Harbour, JW., Murray, TG., Hamasaki, D., et al.[2013]

In a study of 22 retinoblastoma patients treated with intravitreal carboplatin and melphalan, 77% of primary cases and 89% of refractory cases achieved complete control of vitreous seeds after 6 months, indicating the treatment's efficacy.

The treatment was associated with a low incidence of serious side effects, with no cases of orbital invasion, systemic metastasis, or death, suggesting it is a relatively safe option for managing vitreous seeds in retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma. Riazi-Esfahani, H., Masoomian, B., Khodabandeh, A., et al.[2023]

In a study of 21 patients with Group B intraocular retinoblastoma, a chemoreduction regimen using vincristine and carboplatin, along with local therapies, resulted in a 2-year event-free survival rate of 65%, indicating a significant potential for avoiding more invasive treatments like enucleation or external-beam radiotherapy.

All patients showed tumor regression after the first cycle of treatment, and while there were some treatment failures, all patients who experienced these failures were successfully salvaged with additional therapy, highlighting the regimen's overall effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic neoadjuvant chemotherapy for Group B intraocular retinoblastoma (ARET0331): A report from the Children's Oncology Group. Friedman, DL., Krailo, M., Villaluna, D., et al.[2018]

In a study of 76 eyes from 56 patients with group E retinoblastoma, combining chemoreduction (CRD) with low-dose prophylactic external beam radiotherapy (P-EBR) resulted in a significantly higher globe salvage rate (91%) compared to CRD alone (53%) at the 2-year follow-up.

Patients receiving CRD+P-EBR experienced less tumor recurrence and a lower need for enucleation or additional therapeutic radiotherapy, indicating that this combination treatment may be more effective in managing advanced retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoreduction for group E retinoblastoma: comparison of chemoreduction alone versus chemoreduction plus low-dose external radiotherapy in 76 eyes. Shields, CL., Ramasubramanian, A., Thangappan, A., et al.[2015]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-06019

Topotecan Episcleral Plaque for Treatment of ... This single-arm, non-randomized, dose escalation phase I clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan.

2. 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 ...

3. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(25)00173-3/fulltext

Suprachoroidal Injection of Topotecan for Retinoblastoma A single SCI of topotecan (50 μg/0.05 ml) achieved selective tissue distribution of its lactone moiety (retina/plasma, 1377.8) that was 23-fold higher than that ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666914525001733

Suprachoroidal Injection of Topotecan for Retinoblastoma SCI of Topotecan is Nontoxic. Historically, topotecan by various other administration routes seems to be safe, with clinical usage for last 20 years in children ...

5. 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.