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?

In this research study investigators want to learn more about treatment of advanced or recurrent retinoblastoma. For children with retinoblastoma that have an advanced stage of presentation in one eye or if they have failed all conventional treatment, eye removal is considered. This study will investigate the utility of a chemoplaque(s) to salvage eyes involved with retinoblastoma. The goal of the study is to further determine/assess the safety and efficacy and optimal chemotherapy dose 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 safety data exists for Chemoplaque (carboplatin) in humans?

Studies have looked at the safety of carboplatin, a component of Chemoplaque, for treating retinoblastoma. These studies have evaluated its use in the eye and found it can be safe, but there is a risk of retinal toxicity (damage to the retina, the light-sensitive layer at the back of the eye) at higher doses. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Chemoplaque for retinoblastoma?

Research shows that combining different chemotherapy drugs, like carboplatin and melphalan, can help treat retinoblastoma by reducing the need for more invasive treatments like eye removal or radiation. This suggests that Chemoplaque, which may include similar components, could be effective in managing retinoblastoma. ^{2 6 7 8 9}

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

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]

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]

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 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]

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 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]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma. [2023]

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

Systemic neoadjuvant chemotherapy for Group B intraocular retinoblastoma (ARET0331): A report from the Children's Oncology Group. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ocular Survival Following Intravitreal Melphalan as Adjuvant Treatment for Vitreous Retinoblastoma Seeding. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Chemoreduction improves eye retention in patients with retinoblastoma: a report from the German Retinoblastoma Reference Centre. [2015]

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

Chemoreduction for group E retinoblastoma: comparison of chemoreduction alone versus chemoreduction plus low-dose external radiotherapy in 76 eyes. [2015]

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

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial. [2023]

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

A phase I/II study of subconjunctival carboplatin for intraocular retinoblastoma. [2022]

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

Local carboplatin therapy in transgenic murine retinoblastoma. [2013]

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

Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes. [2015]