RATIONALE: 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. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether systemic chemotherapy and subtenon (under the conjunctiva of the eye) carboplatin combined with ophthalmic therapy, with or without low-dose radiation therapy, is effective in treating intraocular (within the eyeball) retinoblastoma.

PURPOSE: Phase III trial to determine the effectiveness of combining systemic chemotherapy and subtenon carboplatin with ophthalmic therapy with or without low-dose radiation therapy in treating children who have intraocular retinoblastoma.

Condition	Treatment or Intervention	Phase
intraocular retinoblastoma	Drug: carboplatin  Drug: etoposide  Drug: filgrastim  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cryosurgery  Procedure: cytokine therapy  Procedure: laser surgery  Procedure: laser therapy  Procedure: phototherapy  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Determine the event-free survival of pediatric patients with group C or D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy and with addition of low-dose radiotherapy in patients with group D intraocular retinoblastoma.

Secondary

• Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies.
• Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence.

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 4 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 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. Beginning 4 weeks after the last course of systemic chemotherapy, patients with group D intraocular retinoblastoma undergo radiotherapy 5 days a week for 2.5 weeks (13 treatments).

Patients are followed every 3 weeks until there is no active tumor seen on a minimum of 3 exams under anesthesia, every 6-8 weeks until 3 years of age, every 3 months until 5 years of age, every 4-6 months until 10 years of age, and then annually thereafter.

PROJECTED ACCRUAL: A total of 69 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  up to  17 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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:
• 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 close to discrete tumor
• Local subretinal seeding < 3 mm from tumor
• 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 cribosa 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

PATIENT CHARACTERISTICS: Age

• Under 18

Performance status

• ECOG 0-2
• Karnofsky 50-100% (over 16 years of age)
• Lansky 50-100% (16 and under)

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT < 2.5 times ULN

Renal

• Creatinine normal for age as follows:
• No greater than 0.8 mg/dL (5 years of age and under)
• No greater than 1.0 mg/dL (6-10 years of age)
• No greater than 1.2 mg/dL (11-15 years of age)
• No greater than 1.5 mg/dL (over 15 years of age)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No other concurrent radiotherapy

Surgery

• See Disease Characteristics

Study chairs or principal investigators

Judith G. Villablanca, MD,  Study Chair,  Children's Hospital Los Angeles   
Timothy G. Murray, MD,  Sylvester Cancer Center   

Study ID Numbers:  CDR0000339627; COG-ARET0231; NCT00072384
Record last reviewed:  April 2004
Last Updated:  December 6, 2004
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072384
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08