Systemic Chemotherapy and Subtenon Carboplatin, and Local Ophthalmic Therapy in Children With Intraocular Retinoblastoma

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00072384
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 30
• Locations: 11
• Arm: 1
• Actual Duration (Months): 170.5
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy in treating children who have intraocular retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy is effective in treating intraocular (within the eyeball) retinoblastoma.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Retinoblastoma	Drug: liposomal vincristine sulfate; Procedure: cryosurgery; Procedure: laser surgery; Drug: carboplatin; Drug: etoposide; Biological: filgrastim	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.

3. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.

4. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy.

5. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma
• Actual Study Start Date: Apr 16, 2007
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy, surgery) Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1.

Drug: liposomal vincristine sulfate; Given IV; Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection ; Procedure: cryosurgery; Application of extreme cold to destroy abnormal or diseased tissue.; Other Names: cryoablation cryosurgical ablation ; Procedure: laser surgery; Surgery using a laser (instead of a scalpel) to cut tissue; Other Names: conventional laser therapy laser therapy, conventional surgery, laser ; Drug: carboplatin; Given IV; Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin ; Drug: etoposide; Given IV; Other Names: EPEG VP-16 VP-16-213 ; Biological: filgrastim; Given subcutaneously; Other Names: G-CSF Neupogen

Outcome Measures

Primary Outcome Measures

1. Group D Eyes - Treatment Failure Within One Year [One year]

   Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.

2. Group C Eyes - Treatment Failure Within One Year [One year]

   Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.

Secondary Outcome Measures

1. Event-free Survival (EFS) [One year after study enrollment]

   Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death.

2. Toxicity Associated With Chemotherapy [From date of enrollment until termination of protocol therapy assessed up to 72 weeks]

   The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.

3. Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence [From the date of enrollment assessed up to 36 months]

   Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected

4. Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement [From the date of enrollment assessed up to 12 months]

   The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Oncology Group	Arcadia	California	United States	91006-3776
2	Southern California Permanente Medical Group	Downey	California	United States	90242
3	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
4	Yale University	New Haven	Connecticut	United States	06520-8032
5	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia	United States	20057
6	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
7	University of Illinois	Chicago	Illinois	United States	60612
8	Duke University Medical Center	Durham	North Carolina	United States	27710
9	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
10	Baylor College of Medicine	Houston	Texas	United States	77030
11	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rima Jubran, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00072384
• Other Study ID Numbers: ARET0231; NCI-2009-00420; CDR0000339627; COG-ARET0231; U10CA098543
• First Posted: Nov 6, 2003
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Retinoblastoma; Carboplatin; Etoposide; Vincristine; Etoposide phosphate

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Period Title: Overall Study
STARTED	30
COMPLETED	21
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Overall Participants	30
Age (months) [Median (Full Range) ]
Median (Full Range) [months]	7.5
Sex: Female, Male (Count of Participants)
Female	16 53.3%
Male	14 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 36.7%
Not Hispanic or Latino	19 63.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 6.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 23.3%
White	12 40%
More than one race	0 0%
Unknown or Not Reported	9 30%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Group D Eyes - Treatment Failure Within One Year
Description	Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Twenty eligible patients had at least one Group D eye to contribute to the analysis. A total of 25 Group D eyes were available for analysis.

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Measure Participants	20
Measure Eyes	25
Mean (Standard Deviation) [Probability of treatment failure]	0.52 (0.102299)

2. Primary Outcome

Title	Group C Eyes - Treatment Failure Within One Year
Description	Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the "Mean" measure type.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Four eligible patients had at least one Group C eye to contribute to the analysis

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Measure Participants	4
Measure Eyes	4
Mean (Standard Deviation) [Probability of treatment failure]	0.25 (0.217)

3. Secondary Outcome

Title	Event-free Survival (EFS)
Description	Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death.
Time Frame	One year after study enrollment

Outcome Measure Data

Analysis Population Description

22 eligible patients were considered for this endpoint.

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Measure Participants	22
Number (95% Confidence Interval) [Percentage probability]	45.45

4. Secondary Outcome

Title	Toxicity Associated With Chemotherapy
Description	The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind.
Time Frame	From date of enrollment until termination of protocol therapy assessed up to 72 weeks

Outcome Measure Data

Analysis Population Description

22 eligible patients were evaluable for the occurrence of grade 3 or higher toxicity of any kind.

Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
Measure Participants	22
Number [Patients]	10

5. Secondary Outcome

Title	Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence
Description	Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected
Time Frame	From the date of enrollment assessed up to 36 months

Outcome Measure Data

Analysis Population Description

1 patient had at least one Group C eye and 11 patients had at least one Group D eye that experienced treatment failure. There were a total of 13 Group D eyes that experienced treatment failure.

Arm/Group Title	Group C Eyes	Group D Eyes
Arm/Group Description	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
Measure Participants	1	11
Retinal seeding and vitreal seeding	0	1
Retinal seeding but no vitreal seeding	1	7
Vitreal seeding but no retinal seeding	0	1
Neither retinal seeding nor vitreal seeding	0	4

6. Secondary Outcome

Title	Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
Description	The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia.
Time Frame	From the date of enrollment assessed up to 12 months

Outcome Measure Data

Analysis Population Description

According to the initial sites of involvement, 4 patients were analyzed in Group C eyes and 20 patients were analyzed for Group D eyes

Arm/Group Title	Group C Eyes	Group D Eyes
Arm/Group Description	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
Measure Participants	4	20
Treatment failure- SRS, SRF, VS	0	3
Treatment failure- SRS; no SRF; no VS	0	0
Treatment failure- SRS and SRF; no VS	0	3
Treatment failure- SRS and VS; no SRF	0	0
Treatment failure- SRF; no SRS; no VS	1	2
Treatment failure- SRF and VS; no SRS	0	3
Treatment failure- VS; no SRS; no SRF	0	2
Treatment failure- No SRS; no VS; no SRF	0	0
No treatment failure- SRS, SRF, VS	0	2
No treatment failure- SRS; no SRF; no VS	0	1
No treatment failure- SRS and SRF; no VS	0	2
No treatment failure- SRS and VS; no SRF	0	2
No treatment failure- SRF; no SRS; no VS	1	2
No treatment failure- SRF and VS; no SRS	0	0
No treatment failure- VS; no SRS; no SRF	1	2
No treatment failure- No SRS; no VS; no SRF	1	1

Adverse Events

Adverse Event Reporting Description	SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Note that while the participant flow demonstrates that 21 completed all cycles of therapy, one additional patient completed fewer than 6 cycles of therapy. The AE profiles are calculated on a per-person basis for the time during which the patient was on therapy.
Arm/Group Title	Treatment (Chemotherapy, Surgery)
Arm/Group Description	Patients receive liposomal vincristine sulfate 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 1prior 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 surgery and/or cryosurgery on day 1. liposomal vincristine sulfate: Given IV cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. laser surgery: Surgery using a laser (instead of a scalpel) to cut tissue carboplatin: Given IV etoposide: Given IV filgrastim: Given subcutaneously
All Cause Mortality
	Treatment (Chemotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Surgery)
	Affected / at Risk (%)	# Events
Total	18/22 (81.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/22 (4.5%)
Ear and labyrinth disorders
Hearing impaired	2/22 (9.1%)
Middle ear inflammation	1/22 (4.5%)
Eye disorders
Eye disorders - Other, specify	2/22 (9.1%)
Infections and infestations
Anorectal infection	1/22 (4.5%)
Bladder infection	1/22 (4.5%)
Device related infection	1/22 (4.5%)
Eye infection	1/22 (4.5%)
Infections and infestations - Other, specify	2/22 (9.1%)
Lung infection	1/22 (4.5%)
Investigations
Neutrophil count decreased	3/22 (13.6%)
Platelet count decreased	1/22 (4.5%)
Skin and subcutaneous tissue disorders
Skin induration	1/22 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior Sponsor approval.