Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT01783535 |
| Other study ID # |
SJRET6 |
| Secondary ID |
NCI-2013-00409 |
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
June 19, 2013 |
| Est. completion date |
January 2028 |
Study information
| Verified date |
March 2024 |
| Source |
St. Jude Children's Research Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
