Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma

The eye(s) will be sterilized prior to injection. Aqueous fluid (0.1-0.15ml) will be
withdrawn and sent for pathology review. Carboplatin diluted in normal saline will be
administered via intravitreal injection under anesthesia once to each eligible eye
approximately every 14 days. Following the injection, triple freeze/thaw cryotherapy is
applied to the injection site and the eye is washed with water. The eye is gently "shaken" in
all directions to evenly distribute the drug.

This trial will use a traditional phase I design for dose de-escalation with two dose levels.
The first 6 patients will be enrolled at dose level 1 and will be observed for dose-limiting
toxicity (DLT) throughout the treatment period up to approximately 5 months after start of
therapy. If 0-2 (of the first 6) participants experience DLT, a second cohort of 6 patients
will be enrolled at the same dose level 1. Study accrual would be completed at 12.

However, if 3 or more of the first 6 patients experience DLT at dose level 1, the dose level
would be de-escalated to level -1 and 6 patients enrolled at this level (dose -1). If 0-2
patients experience DLT at dose level -1, a second cohort of 6 patients will be enrolled at
dose level -1, and the study accrual would be complete. If 3 or more patients experience DLT
at dose level -1, accrual would also be complete.

Inclusion Criteria:

- Refractory or recurrent retinoblastoma with vitreous seeding meeting eligibility
criteria by ultrasonic biomicroscopy performed during examination under anesthesia
(EUA) by an ophthalmologist:

- At least three consecutive clock hours of disease-free, attached peripheral
retina through which the intraocular injection may be administered.

- Absence of invasion in anterior and posterior chamber.

- Absence of anterior hyaloid detachment.

- Absence of retinal detachment at the entry site.

- Absence of tumor at the entry site.

- ECOG Performance Score must be ≤ 2 within two weeks prior to registration.

- Participants must have an adequate liver function, as defined by bilirubin ≤3 x upper
limit of normal (ULN), and SGOT and SGPT ≤3 x ULN.

- Participants must have adequate renal function as defined by serum creatinine ≤3 x ULN
for age.

- Legal guardians must sign an informed consent indicating that they are aware of this
study, the possible benefits, and toxic side effects. Legal guardians will be given a
signed copy of the consent form.

Exclusion Criteria:

- Presence of metastatic disease or gross orbital involvement.

- Participants must not have an invasive infection at time of protocol entry.

- Inability or unwillingness of research participant or legal guardian/representative to
give written informed consent.