Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma

  • STATUS
    Recruiting
  • End date
    Jan 15, 2028
  • participants needed
    200
  • sponsor
    St. Jude Children's Research Hospital
Updated on 15 September 2022
renal function
cyclophosphamide
filgrastim
vincristine
cryotherapy
etoposide
doxorubicin
neutrophil count
carboplatin
mesna
beam radiation
nervous
topotecan
intraocular retinoblastoma
unilateral 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.

Description

Participants will be stratified into four main treatment groups, depending on whether retinoblastoma is present in one or both eyes and disease grouping [early or advanced, Reese-Ellsworth (R-E) group I-V, and International Classification A-E]. Additionally, participants will be invited to participate in exploratory research objectives that address cognitive and functional development of children with retinoblastoma, the pharmacokinetics of topotecan in young children, and evaluation of ototoxicity, including genetic analysis.

TREATMENT PLAN

STRATUM A:

  • Children ≥ or equal to 6 months old at time of enrollment - 8 courses of vincristine and carboplatin, given at 3-4 week intervals.
  • Infants < 6 months old at time of enrollment - Therapy will consist of six courses of chemotherapy; three courses of vincristine and carboplatin, given at 3-4 week intervals, alternating with 3 cycles of vincristine and topotecan, given at 3-4 week intervals.

Focal treatments will be administered at the discretion of the treating team. Focal therapies will include cryotherapy, laser photocoagulation, thermo-therapy and plaque radiotherapy.

STRATUM B:

  • Participants without extensive sub-retinal (SR) seeding, treatment will consist of two up-front courses of vincristine and topotecan, given at 3-4 week intervals.
  • Participants without SR seeding: ≥ or equal to partial response after 2 cycles, will receive three additional courses of vincristine-topotecan (VT) and six courses of vincristine-carboplatin, given at 3-4 week intervals.
  • Participants without SR seeding and < partial response after 2 cycles VT will receive 6 courses of vincristine-carboplatin-etoposide (VCE), given at 3-4 week intervals.
  • Participants with extensive sub-retinal (SR) seeding will receive two up-front courses of subconjunctival (also called subtenon or periocular) CARBOplatin and systemic topotecan, given at 3-4 week intervals.
  • Participants with SR seeding: > or equal to partial response after 2 cycles will receive three additional courses of vincristine-topotecan, and six courses of vincristine-carboplatin, given at 3-4 week intervals.
  • Participants with SR seeding: < partial response after 2 cycles will receive 6 courses of VCE, given at 3-4 week intervals.

Focal treatments will be administered at the discretion of the treating team. Focal therapies will include cryotherapy, laser photocoagulation, thermo-therapy and plaque radiotherapy.

STRATUM C:

Participants with unilateral (unifocal or multifocal) advanced (R-E IV-V and IC D-E) intraocular disease will undergo enucleation. Adjuvant therapy will be based on

histopathology
  • low risk participants: Participants in whom the enucleated eye does not show extra-retinal disease (see definition of intermediate and high risk below); will not receive any additional treatment.
  • intermediate risk participants: Participants in whom the enucleated eye shows presence of tumor in the anterior chamber, invasion of the ciliary body/iris, massive invasion of the choroid, and invasion of the optic nerve beyond the lamina cribrosa with concomitant invasion of the choroid, will receive 4 courses of adjuvant chemotherapy with vincristine-carboplatin-doxorubicin (VCD).
  • high risk participants: Participants in whom the enucleated eye shows involvement of the sclera, or involvement of the optic nerve at the level of the cut-end, will be treated with 6 courses of chemotherapy, with alternating courses of VCE and VCD.
  • High-risk participants with extra-ocular extension (i.e. tumor extending beyond the sclera/cornea or beyond the cut end of the optic nerve) will be candidates for external-beam radiation therapy (EBRT) to the entire orbit, including the optic nerve, administered after 2 or 3 courses of treatment. Patients with extra-ocular extension may be considered for enrollment on an alternative therapeutic protocol for metastatic retinoblastoma (or best clinical management).

STRATUM D:

Management of participants with bilateral retinoblastoma is often complex; and some participants will have one eye enucleated upfront due to advanced disease. The decision for enucleation will be made after thorough consideration by the treating team. The treatment of the remaining eye will depend on a combination of two factors: a) R-E group of the remaining eye, and b) Histology of the enucleated eye. Though we have accumulated some information regarding the use of vincristine, cyclophosphamide, and doxorubicin in the treatment of intraocular retinoblastoma, it is not considered standard of care. Therefore, participants with intermediate and high risk features will be treated with 6 courses of vincristine, carboplatin, and etoposide (VCE). Those participants in whom the enucleated eye shows only low risk histology will be eligible to proceed with either stratum A or stratum B therapy. For those receiving stratum B therapy, consideration of periocular carboplatin will be allowed. External beam or proton beam radiation therapy will be considered for patients with extra-ocular extension.

Focal treatments will be administered at the discretion of the treating team. Focal therapies will include cryotherapy, laser photocoagulation, thermo-therapy and plaque radiotherapy.

Details
Condition Retinoblastoma
Treatment cyclophosphamide, Topotecan, filgrastim, etoposide, carboplatin, vincristine, vincristine, PEG-filgrastim, focal therapy, MESNA, MESNA, doxorubicin, doxorubicin, enucleation, external beam radiation or proton beam radiation
Clinical Study IdentifierNCT01783535
SponsorSt. Jude Children's Research Hospital
Last Modified on15 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Newly diagnosed, untreated intraocular retinoblastoma. Participants previously diagnosed with unilateral retinoblastoma treated surgically, with focal therapy or needing chemotherapy who develop asynchronous involvement of the contralateral eye, or patients with unilateral retinoblastoma treated only with enucleation or focal therapy who develop asynchronous involvement of the contralateral eye, will be eligible for study
ECOG Performance Score must be ≤ 2 within two weeks prior to registration
Participants must have an adequate liver function, as defined by bilirubin ≤ to 3X upper limit of normal (ULN), and SGOT and SGPT ≤ to 3X ULN
Participants must have adequate renal function as defined by serum creatinine ≤ to 3X ULN for age
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

Exclusion Criteria

Previously treated participants
Presence of metastatic disease or gross (residual) orbital involvement
Participants must not have an invasive infection at time of protocol entry
Inability or unwillingness of research participant or legal guardian/representative to give written informed consent
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note