Carboplatin + Topotecan for Retinoblastoma

Recruiting in Palo Alto (17 mi)

Overseen byCarlos Rodriguez-Galindo, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for children with newly diagnosed, untreated intraocular retinoblastoma. It includes those who had unilateral retinoblastoma and now have it in the other eye. They must be able to perform daily activities (ECOG ≤ 2) and have normal kidney and liver function. Those with previous treatments, metastatic disease, active infections or unable to consent are excluded.

Inclusion Criteria

I have been mostly active and able to care for myself in the last two weeks.

I have a new, untreated eye cancer or my other eye has now been affected.

Legal guardians must sign an informed consent indicating that they are aware of this study, the possible benefits, and toxic side effects. Legal guardians will be given a signed copy of the consent form.

+2 more

Exclusion Criteria

Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

My cancer has spread to other parts of my body or affects my eye socket.

I do not have a serious infection right now.

+1 more

Participant Groups

The study tests how well advanced intraocular retinoblastoma responds to direct-eye chemotherapy (carboplatin) plus systemic topotecan. It also uses various therapies like cryotherapy, thermotherapy, radiation therapy, surgery or enucleation if necessary while trying to preserve vision.

4Treatment groups

Experimental Treatment

Group I: Stratum DExperimental Treatment9 Interventions

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.

Group II: Stratum CExperimental Treatment9 Interventions

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

Group III: Stratum BExperimental Treatment7 Interventions

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.

Group IV: Stratum AExperimental Treatment6 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.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Paraplatin for: