Episcleral Topotecan for Treatment of Group D Retinoblastoma

Summary

Participation Requirements

Description

Treatment of eyes with advanced intraocular retinoblastoma remains a challenge. The historic standard of care for patients with unilateral disease is enucleation and for those with bilateral disease, a variety of modalities have been tried. These include radiation therapy, systemic chemotherapy, per...

Treatment of eyes with advanced intraocular retinoblastoma remains a challenge. The historic standard of care for patients with unilateral disease is enucleation and for those with bilateral disease, a variety of modalities have been tried. These include radiation therapy, systemic chemotherapy, periocular administration of chemotherapy, selective intra-arterial chemotherapy, and intravitreal chemotherapy. Unfortunately, all of these modalities are associated with significant morbidity and investigators are looking for new ways to treat these patients either with novel directed drug delivery methods or with new less toxic agents. This study will evaluate the feasibility and toxicity of topotecan delivered directly to the eye using a novel episcleral implant (also referred to as an episcleral reservoir). Children with newly diagnosed unilateral retinoblastoma classified as Group D according to the International Group Classification System will be eligible for the study if: (1) they have had no previous treatment, and (2) primary enucleation is a treatment recommendation. All enrolled eyes during a day-1 baseline EUA will be fitted with one or two episcleral implants (reservoirs) containing sustained release formulations of topotecan HCl as the only therapy for a four-week study period. Episcleral Topotecan will be supplied sterile and requires no manipulation other than placement on the eye. At a two-week EUA on day-15 of the four-week study period, if tumor response criteria are not met or if there is DLT, the Episcleral Reservoir will be removed and the patient will be off study and alternate interventions begun. In the event of enucleation remaining drug concentrations will be determined in the reservoir(s) as well as plasma concentration levels (anticipated to be below limits of detection based on preclinical studies). If tumor response criteria are met, the eye is eligible for continuing for the final two weeks of the study if there is no local, systemic or intraocular dose limiting toxicity (DLT) as defined in this protocol. At the end of the 4-week study period on study day-29 the third and final EUA will be conducted and tumor response and toxicity assessed. At that time, all reservoirs are removed and the eye is off study. Drug concentration/levels are determined in the removed reservoir(s), plasma, and tumor in the event of enucleation. The child and the eye shall then be treated at the discretion of the managing ophthalmologist and oncologist.

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