A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

Inclusion Criteria:

• Patient must be < 18 years of age at enrollment

• Patient must have newly diagnosed intraocular (localized) retinoblastoma and meetone of the following criteria:

• Unilateral Group D retinoblastoma with vitreous seeding; OR

• Bilateral retinoblastoma with worst eye Group D, with vitreous seeding presentand the contralateral eye is Group A-C; OR

• Bilateral Group D retinoblastoma with at least one eye with vitreous seeding;OR

• Bilateral retinoblastoma with one Group D eye with vitreous seeding and oneGroup E eye where the Group E eye has been enucleated prior to any therapy.Note exclusion for high-risk features

• Bilateral retinoblastoma with one Group D eye with vitreous seeding and oneGroup E eye where the Group E eye has not been enucleated prior to any therapyat the discretion of the treating physician. Note exclusion for patients withevidence of metastatic or extra orbital spread

• Patients must have a performance status corresponding to Eastern CooperativeOncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years ofage and Lansky for patients =<16 years of age

• Peripheral absolute neutrophil count (ANC) >= 750/uL (must be performed within 7days prior to enrollment unless otherwise indicated)

• Platelet count >= 75,000/uL (transfusion independent) (must be performed within 7days prior to enrollment)

• A serum creatinine based on age/gender as follows (must be performed within 7 daysprior to enrollment; must be repeated prior to the start of protocol therapy if > 7days have elapsed from their most recent prior assessment):

• 1 month to < 6 months = 0.4 (male and female)

• 6 months to < 1 year = 0.5 (male and female)

• 1 to < 2 years = 0.6 (male and female)

• 2 to < 6 years = 0.8 (male and female)

• 6 to < 10 years = 1.0 (male and female)

• 10 to < 13 years = 1.2 (male and female)

• 13 to < 16 years = 1.5 (male) and 1.4 (female)

• >= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinineclearance >= 70 mL/min/1.73 m^2 OR - a glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclearblood sampling method OR direct small molecule clearance method (iothalamate orother molecule per institutional standard)

• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimatesare not acceptable for determining eligibility

• For patients < 1 month of age, serum creatinine levels must be < 1.5 x thetreating institution's creatinine upper limit of normal (ULN) for patients < 1 month of age or the creatinine clearance or radioisotope GFR must be >= 70 mL/min/1.73 m^2

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performedwithin 7 days prior to enrollment; must be repeated prior to the start of protocoltherapy if > 7 days have elapsed from their most recent prior assessment)

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135U/L (must be performed within 7 days prior to enrollment; must be repeated prior tothe start of protocol therapy if > 7 days have elapsed from their most recent priorassessment)

• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to thevalue of 45 U/L

Exclusion Criteria:

• Patients with evidence of metastatic or extra-orbital spread

• Patients must not have an invasive infection at time of protocol entry

• Patients must not have had any prior anti-cancer therapy other than cryotherapyand/or laser therapy (green or infrared) to the study eye(s) and non-study eye,including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque,brachytherapy, or radiation therapy.

• Note: A study eye is defined as being Group D with vitreous seeding. Patientsmay have had enucleation of one eye as long as the remaining eye is Group Dwith vitreous seeds

• Patients with bilateral disease who undergo enucleation of a Group E eye prior toinitiation of therapy and show evidence of high-risk histopathology features in theenucleated eye. High-risk histopathology includes choroid involvement >= 3 mm, postlamina optic nerve involvement, full thickness scleral invasion or optic nerveinvasion to the cut end

• Female patients who are pregnant since fetal toxicities and teratogenic effects havebeen noted for several of the study drugs. A pregnancy test is required for femalepatients of childbearing potential

• Lactating females who plan to breastfeed their infants

• Sexually active patients of reproductive potential who have not agreed to use aneffective contraceptive method for the duration of their study participation

• All patients and/or their parents or legal guardians must sign a written informedconsent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met