At a glance
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Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma
In Brief
A Phase 2 clinical trial evaluating vincristine, topotecan, and 10 other interventions for Retinoblastoma. Active but no longer recruiting, targeting 174 participants across 1 site.
Signals
Detailed Summary
The primary objective of this protocol is to evaluate the response rate of bilateral disease participants who have at least one eye with advanced intra-ocular retinoblastoma (stratum B) using upfront therapy with chemotherapy delivered directly to the eye. The main biology objective is to improve our understanding of the biology and tumorigenesis (how tumor develops) of retinoblastoma when biology specimens are available. As clinicians, the primary goal of the investigators for children with retinoblastoma is to provide optimal therapy using multiple treatment approaches \[chemotherapy (into the vein and directly into membrane of eyeball), cryotherapy (freeze and destroy tumor), thermotherapy (laser or heat to destroy tumor), radiation therapy, and surgical removal of eye if needed) in an attempt to preserve the eye and vision whenever possible, while still curing the disease. Therefore, all children with non-metastatic retinoblastoma at St. Jude will be offered enrollment on this study. PRIMARY OBJECTIVE: * To evaluate the response (complete + partial response) rate of bilateral disease participants who have at least one eye with advanced intraocular retinoblastoma (Stratum B) to two upfront courses of therapy consisting of subconjunctival carboplatin and systemic topotecan. SECONDARY OBJECTIVES: * To evaluate the ocular survival of eyes and event-free survival of participants by strata. * To prospectively analyze intraocular disease tissue for participants with at least one eye undergoing enucleation in order to identify the mechanism of RB1 bi-allelic inactivation. Participants may undergo upfront enucleation (due to advanced disease at diagnosis) or may receive enucleation due to progressive disease during protocol therapy.
Study Details
Timeline
Arms & Interventions
Participants with early bilateral or unilateral (unifocal or multifocal) retinoblastoma (R-E I-III, IC A-B; R-E IV with IC A or B; or IC C with limited sub-retinal seeding), and participants with bilateral disease in whom the advanced eye has been enucleated upfront (without any high risk histopathology) and the remaining eye has early stage disease (as defined above). Interventions (see detailed description): vincristine, carboplatin, topotecan, filgrastim or PEG-filgrastim, and focal therapy, including cryotherapy, laser photocoagulation, thermo-therapy, plaque radiotherapy.
Participants considered candidates for conservative management including those: 1. Participants with bilateral retinoblastoma who have R-E IV-V and IC D in one eye 2. Participants with advanced unilateral (unifocal or multifocal) retinoblastoma (R-E IV-V and IC D-E) who demonstrate foveal sparing by the tumor during EUA. Due to foveal sparing, these patients have potential for vision preservation. Interventions (see Detailed Description): vincristine, topotecan, carboplatin, etoposide, filgrastim or PEG-filgrastim and focal therapy, including cryotherapy, laser photocoagulation, thermo-therapy, plaque radiotherapy.
Participants with advanced (R-E IV-V and IC D-E) unilateral retinoblastoma who require upfront enucleation. Participants will be assessed and treated by low, intermediate or high risk. Interventions (see Detailed Description): vincristine, cyclophosphamide, MESNA, doxorubicin, etoposide, carboplatin, filgrastim or PEG-filgrastim, enucleation
Participants with bilateral retinoblastoma who may require upfront enucleation for one eye due to advanced disease (R-E IV-V and IC E). Interventions (see Detailed Description): vincristine, carboplatin, topotecan, etoposide, enucleation, filgrastim or PEG-filgrastim, focal therapy, including cryotherapy, laser photocoagulation, thermotherapy (and thermo-chemotherapy) and episcleral plaque brachytherapy, and external beam radiation or proton beam radiation in select cases.
Interventions
Given via minibag/gravity flow.
Given IV over 30 minutes.
Given subcutaneously 24-36 hours after chemotherapy for 7-10 days, until absolute neutrophil count (ANC) is \>2,000/µL on one occasion after the expected nadir.
Given subcutaneously 24-36 hours after chemotherapy for 7-10 days, until ANC is \>2,000/µL on one occasion after the expected nadir.
Given IV over 60 minutes. Given periocular (subtenon/subconjunctival).
Focal treatments will be administered at the discretion of the treating team to strata A, B and D. In select cases of very early stage retinoblastoma (Stratum A), participants may receive focal therapies only and chemotherapy will be held at the discretion of the treating team. If there is any evidence of progression or unsatisfactory results, the participant will begin chemotherapy as per Stratum A. For selected participants an effort will be made to perform sequential chemo-thermotherapy. In these cases, carboplatin will be administered one or two hours prior to thermotherapy.
Given IV. Participants who cannot tolerate etoposide may be given etoposide phosphate (Etopophos(R)).
Given IV.
Given IV before CYCLO and at 3, 6 and 9 hours after CYCLO.
Given IV on Day 1 of Cycles 2, 4 and 6 in Stratum C high-risk.
Eye removal due to advanced disease in Strata C and D participants.
EBRT or proton beam radiation will be administered to any eye in which the disease is considered to be not controllable with focal treatments alone, and in participants with enucleated eyes in which high risk of orbital and/or central nervous system disease is documented histologically (high-risk group with disease extension beyond the sclera or cornea, or beyond the cut end of the optic nerve). EBRT will be administered using standard techniques practices with the objective of limiting dose to normal tissues including the hypothalamic-pituitary unit, supratentorial brain, orbit, cochleae and contralateral eye when indicated. Participants will be evaluated on an individual basis to determine whether they might benefit from referral for proton therapy.