Retinoblastoma Phase II Expanded Access Clinical Trial

Inclusion Criteria:

• Age: Participants must be < 8 years of age.

• Diagnosis and Treatment. Participants must have: Group D or earlier-stageintraocular retinoblastoma in which enucleation is a recommended therapy, OR Activeresidual or recurrent intraocular retinoblastoma in at least one eye followingcompletion of first- line therapy (focal therapy for IIRC Group A eyes, or systemicor intra-arterial chemotherapy).

If both eyes require treatment, there will receive independent and individual treatment. Non-study eye will be treated by standard of care, with only focal therapy during the Study Period, if required.

• Must have demonstrated intraocular calcium in the tumor-containing eye by ophthalmicultrasound or by neuroimaging as part of standard retinoblastoma diagnosis.

• Study eye must have vision potential, at least light perception vision in thetumor-bearing eye either with pupil response testing or demonstration of avoidancebehavior to light presentation in the affected eye, and no clinical featuressuggestive of high risk of extraocular extension.

• Performance Level: Lansky ≥ 50 (<16 years of age); Karnofsky performance scale of ≥50 (≥16 years of age).

• Organ Function Requirements:

1. Adequate Bone Marrow Function defined as:

• Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3 (transfusion independent, defined as notreceiving platelet transfusions for at least 7 Days prior to enrollment)
• Hemoglobin ≥ 8.0 g/dL at baseline (may receive RBC transfusions)

2. Adequate Renal Function defined as:

• Creatinine clearance or radioisotope GFR ≥70ml/min/1.73 m2 or
• A serum creatinine based on age/gender as follows:Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5

1. to < 2 years 0.6 0.6

2. to < 6 years 0.8 0.8 6 to < 7 years 1 1The threshold creatinine values in this Table were derived from the Schwartzformula for estimating GFR utilizing child length and stature data published bythe CDC.

3. Adequate Liver Function defined as:

• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
• SGPT (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
• Serum albumin ≥ 2 g/dL.

4. Pregnancy prevention. Females of reproductive potential must agree to the useof highly effective contraception during study participation and for anadditional 40 days after the end of Episcleral Topotecan administration.

5. Informed consent. All participants and/or their parents or legally authorizedrepresentatives must have the ability to understand and the willingness to signa written informed consent. Assent, where appropriate, will also be obtained.

Exclusion Criteria:

• Disease status. Participants known to have any of the following are excluded:

1. tumor involving the optic nerve rim

2. clinical or EUA evidence of extraocular extension

3. evidence of metastatic retinoblastoma

4. existing neuroimaging showing suspicion of, or definitive, optic nerveinvasion, trilateral retinoblastoma or extra-ocular extension.

• Allergy. Participants with reported allergy to topotecan, camptothecin orderivatives thereof are excluded.

• Concomitant treatment. Participants who have received chemotherapy, other focalretinoblastoma therapy or any other investigational agent within 3 weeks ofEpiscleral Topotecan placement are not eligible.

• Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrentillness that, in the investigator's opinion, would put the participant at undue riskor limit compliance with the study requirements, are not eligible.

• Febrile illness. Participants with clinically significant febrile illness (asdetermined by the investigator) within one week prior to initiation of protocoltherapy are excluded.

• Pregnancy and lactation. Females of reproductive potential must have a negativeserum pregnancy test within 72 hours prior to initiation of protocol therapy. Due tothe unknown but potential risk for adverse events (AEs) in nursing infants secondaryto treatment of the mother with the study agents, breastfeeding must be discontinuedif the mother is treated on study.

• Compliance. Any condition of diagnosis that could in the opinion of the PrincipalInvestigator or delegate interfere with the participant's ability to comply with thestudy instruction, might confound the interpretation of the study results, or putthe participant at risk.