Topotecan Episcleral Plaque for Treatment of Retinoblastoma

Inclusion Criteria:

1. Age. Participants must be <18 years of age.

2. Diagnosis and Treatment. Participants must have: (i) active residual or recurrentintraocular retinoblastoma following completion of first-line therapy (chemotherapy,systemic or intra-arterial, focal therapy or brachytherapy), or (ii) unilateralGroup B, C, D or cT1b, cT2 retinoblastoma at diagnosis with no previous treatment.

3. One eye will be the Study Eye. When participants have two eyes with retinoblastoma,the eye with worst disease or best vision potential will be designated the StudyEye. There will only be one eye per child treated in this Phase I study, sincetreatment of two eyes would double the systemic dose of drug. The Non-study eye willbe treated by standard of care, with only focal therapy during the Study Period, ifrequired.

4. Disease status. Study eye must have vision potential and no clinical featuressuggestive of high risk of extraocular extension.

5. Performance status. Lansky play score ≥ 50 if <16 years of age; Karnofskyperformance scale of ≥ 50 if ≥16 years of age (Appendix I)

6. Organ function:

7. Adequate bone marrow function and platelet count

8. Adequate renal function

9. Adequate liver function

10. Pregnancy prevention. Females of reproductive potential must agree to the use ofhighly effective contraception during study participation and for an additional 40days after the end of the Chemoplaque administration

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

Exclusion Criteria:

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

2. clinical or EUA evidence of extraocular extension

3. known metastatic disease status and intercurrent illness

4. existing clinical and neuroimaging showing suspicion of, or definitive,

5. Allergy. Participants with reported allergy to topotecan, camptothecin orderivatives thereof.

6. Concomitant treatment. Participants may not receive chemotherapy or other focalretinoblastoma therapy or any other investigational agent within 3 weeks of theplacement and removal of the Chemoplaque, nor while the Chemoplaque is in situ.

7. 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.

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

9. 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.

10. 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.