A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
N/A
17 Years
Both
Intraocular Retinoblastoma
Trial Information
A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
PRIMARY OBJECTIVES:
I. Determine the event-free survival at 12 months of pediatric patients' eyes with group D
intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine,
carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event
defined for each eye individually as needed for nonprotocol therapy including nonprotocol
chemotherapy, enucleation or any external-beam radiation)
SECONDARY OBJECTIVES:
I. Determine the event-free survival at 12 months of pediatric patients' eyes with group C
retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide,
vincristine, subtenon carboplatin, and local ophthalmic therapy.
II. Determine the acute and long-term toxic effects of these regimens in these patients,
including visual outcome and incidence of secondary malignancies.
III. Determine the patterns of failure in patients treated with these regimens, in terms of
vitreous vs retinal vs both as sites of recurrence.
IV. Determine predictors of failure including findings at the on study examination under
anesthesia and response status after six courses of chemotherapy.
V. Determine the percentage of group C and D eyes separately that can be preserved without
enucleation after failing protocol therapy.
OUTLINE: This is a multicenter study.
Patients receive vincristine IV over 1 minute on day 1 and carboplatin IV over 1 hour and
etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF)
subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients
receive subtenon carboplatin to each group C or D eye on day 0 or 1 prior of courses 2-4
only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of
extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic
chemotherapy, patients undergo local ophthalmic therapy comprising local laser and/or
cryotherapy on day 1.
Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every
6 months until 5 years of age, and then annually for up to 10 years.
Inclusion Criteria:
- Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular
retinoblastoma by ophthalmologic examination, defined by the International
Classification System for Intraocular Retinoblastoma as the following:
- Group C: Discrete localized disease with minimal subretinal and/or vitreous
seeding
- Subretinal fluid, without prior or concurrent seeding, involving ≤ one
quarter of the retina
- Local fine vitreous seeding may be present close to discrete tumor
- Local subretinal seeding < 3 mm from tumor
- Group D: Diffuse disease with significant vitreous and/or subretinal seeding
- Tumor(s) may be massive or diffuse
- Subretinal fluid, without prior or concurrent seeding, involving up to
total retinal detachment
- Diffuse or massive vitreous disease may include "greasy" seeds or avascular
tumor masses
- Diffuse subretinal seeding may include subretinal plaques or tumor nodules
- Prior enucleation of 1 eye allowed provided the remaining eye is group C or D
- No tumor present on histologic examination at the cut end of the optic nerve on any
eye enucleated prior to study entry
- Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is
allowed
- No extraocular retinoblastoma clinically or by MRI of brain and orbits with and
without gadolinium or CT scan with and without contrast of brain and orbits
- No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or
any other additional test
- Performance status - Karnofsky 50-100% (over 16 years of age)
- Performance status - Lansky 50-100% (16 and under)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST and ALT < 2.5 times ULN for age
- Creatinine adjusted according to age as follows:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
- Creatinine clearance or radioisotope glomerular filtration rate at least 70
mL/min/1.73m^2
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Negative pregnancy test in postmenarchal females
- No prior chemotherapy
- No other concurrent chemotherapy
- No prior radiotherapy
- No other concurrent radiotherapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Proportion of failure-free survival of patients with group C and/or D retinoblastoma
Outcome Description:
The observed failure proportion for group D eyes will be compared to the historical proportion of 0.70 using a method suggested by Rosner. The proportion of group C eyes that fail will be compared to the historical probability of 0.40 using the same method.
Outcome Time Frame:
At 1 year
Safety Issue:
No
Principal Investigator
Rima Jubran
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
ARET0231
NCT ID:
NCT00072384
Start Date:
April 2007
Completion Date:
Related Keywords:
- Intraocular Retinoblastoma
- Retinoblastoma
Name | Location |
|---|---|
| Baylor College of Medicine | Houston, Texas 77030 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Duke University Medical Center | Durham, North Carolina 27710 |
| Yale University | New Haven, Connecticut 06520 |
| M D Anderson Cancer Center | Houston, Texas 77030 |
| Lombardi Comprehensive Cancer Center at Georgetown University | Washington, District of Columbia 20057 |
| University of Illinois | Chicago, Illinois 60612 |
| Children's Oncology Group | Arcadia, California 91006-3776 |
| Children's Healthcare of Atlanta - Egleston | Atlanta, Georgia 30322 |
