RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor tumor from dividing so they stop growing or die. It is not yet known whether neoadjuvant chemotherapy combined with standard local ophthalmic therapy is effective in treating intraocular retinoblastoma.

PURPOSE: This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma.

Condition	Treatment or Intervention	Phase
intraocular retinoblastoma	Drug: carboplatin  Drug: iodine I 125  Drug: ruthenium Ru 106  Drug: vincristine  Procedure: chemotherapy  Procedure: cryosurgery  Procedure: isotope therapy  Procedure: laser therapy  Procedure: neoadjuvant therapy  Procedure: phototherapy  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy.

Secondary

• Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.
• Correlate response rate with event-free survival in patients treated with this regimen.
• Determine the incidence of toxic effects in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106.

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

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study within 3.5 years.

Ages Eligible for Study:  up to  5 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:
• Group B tumor(s) in 1 eye
• Group B tumor(s) in both eyes
• Group A tumor in 1 eye and Group B tumor(s) in the other eye
• Group E tumor in 1 eye that has been enucleated and Group B tumor(s) in the remaining eye at the time of enucleation of the Group E tumor
• Defined by the International Classification System for Intraocular Retinoblastoma as follows:
• Group A: Small tumors (≤ 3 mm) confined to the retina meeting the following criteria:
• More than 3 mm from fovea
• More than 1.5 mm from optic disk
• Group B: Tumors more than 3 mm meeting the following criteria:
• Confined to the retina in any location
• Clear subretinal fluid ≤ 6 mm from tumor margin
• Group E: Must have visual potential OR at least 1 of the following must be present:
• Tumor in the anterior segment
• Tumor in or on the ciliary body
• Neovascular glaucoma
• Vitreous hemorrhage obscuring the tumor of significant hyphema
• Phthisical or pre-phthisical eye
• Orbital cellulitis-like presentation
• Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks
• No choroidal and/or optic nerve invasion past the lamina cribosa
• No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan
• No tumor present on histological exam at the cut end of the optic nerve for any Group E eye enucleated before study entry

PATIENT CHARACTERISTICS: Age

• 5 and under

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

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

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70mL/min OR
• Creatinine ≤ 0.8 mg/dL

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, including intensity-modulated stereotactic, or proton beam radiotherapy

Surgery

• Prior enucleation of one eye allowed provided the remaining eye is Group B
• No concurrent enucleation

Other

• No prior local ophthalmic therapy for retinoblastoma
• No other prior therapy for retinoblastoma
• No local therapy during chemotherapy course 1

Study chairs or principal investigators

Debra Friedman, MD,  Study Chair,  Children's Hospital and Medical Center - Seattle   

Study ID Numbers:  CDR0000355721; COG-ARET0331; NCT00079417
Record last reviewed:  April 2004
Last Updated:  March 10, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079417
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08