Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma

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.

Conditions

• Retinoblastoma

Interventions

DRUG

vincristine

Given via minibag/gravity flow.

DRUG

topotecan

Given IV over 30 minutes.

DRUG

filgrastim

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.

DRUG

PEG-filgrastim

Given subcutaneously 24-36 hours after chemotherapy for 7-10 days, until ANC is \>2,000/µL on one occasion after the expected nadir.

DRUG

carboplatin

Given IV over 60 minutes. Given periocular (subtenon/subconjunctival).

OTHER

focal therapy

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.

DRUG

etoposide

Given IV. Participants who cannot tolerate etoposide may be given etoposide phosphate (Etopophos(R)).

DRUG

cyclophosphamide

Given IV.

DRUG

MESNA

Given IV before CYCLO and at 3, 6 and 9 hours after CYCLO.

DRUG

doxorubicin

Given IV on Day 1 of Cycles 2, 4 and 6 in Stratum C high-risk.

PROCEDURE

enucleation

Eye removal due to advanced disease in Strata C and D participants.

RADIATION

external beam radiation or proton beam radiation

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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Carlos Rodriguez-Galindo, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-06-19

Primary Completion

2023-03-17

Completion

2028-01-31

FDA Drug

Yes

Countries

• United States

Study Locations